BACKGROUND: The OraQuick In-Home HIV self-test represents a fast, inexpensive, and convenient method for users to assess their HIV status. If integrated thoughtfully into existing testing practices, accompanied by efficient pathways to formal diagnosis, self-testing could enhance both HIV awareness and reduce HIV incidence. However, currently available self-tests are less sensitive, particularly for recent infection, when compared to gold-standard laboratory tests. It is important to understand the impact if some portion of standard testing is replaced by self-tests. We used a compartmental model to evaluate the effects of self-testing in diverse scenarios among gay, bisexual and other men who have sex with men (MSM) in the United States for the period 2020-2030, and to understand which scenarios maximize the advantages of self-testing. METHODS: We introduced a novel 4-compartment model for HIV self-testing. We employed the model under different screening rates, self-test proportions, and delays to diagnosis for those identified through self-tests to determine the potential effects of self-testing on HIV incidence and awareness of status when applied to the US MSM population. We studied scenarios in which self-tests supplement laboratory-based tests, with no replacement, and scenarios in which some replacement occurs. We also examined how future improvements in self-test sensitivity may affect our results. RESULTS: When HIV self-tests are supplemental rather than substitutes for laboratory-based testing, self-testing can decrease HIV incidence among MSM in the US by up to 10 % and increase awareness of status among MSM from 85 % to 91 % over a 10-year period, provided linkage to care and formal diagnosis occur promptly following a positive self-test (90 days or less). As self-tests replace a higher percentage laboratory-based testing algorithms, increases in overall testing rates were necessary to ensure reductions in HIV incidence. However, such needed increases were relatively small (under 10 % for prompt engagement in care and moderate levels of replacement). Improvements in self-test sensitivity and/or decreases in the detection period may further reduce any necessary increases in overall testing by up to 40 %. CONCLUSIONS: If properly utilized, self-testing can provide significant long-term reductions to HIV incidence and improve awareness of HIV status. Ensuring that self-testing increases overall testing and that formal diagnosis and engagement in care occur promptly following a positive self-test are necessary to maximize the benefits of self-testing. Future improvements in self-test sensitivity and reductions in the detection period would further reduce HIV incidence and the potential risks associated with replacing laboratory tests with self-tests.

OBJECTIVE: Depression is prevalent among persons with HIV (PWH) and is associated with poorer adherence and lack of viral load suppression (VLS). When treated for depression, PWH are more likely to stay in HIV care and adhere to medications; however, for many PWH, depression is not adequately diagnosed or treated. We adapted Progression and Transmission of HIV (PATH 3.0), a U.S. agent-based dynamic stochastic simulation model, by incorporating a continuum of depression care and estimating the impact on VLS of an enhanced depression diagnosis and care scenario (EDC). METHODS: We compared EDC-whereby every PWH is assessed for depression, gets treatment if diagnosed, and of those, half achieve remission-to a status quo scenario (SQ) on VLS. Based on published findings, assumptions for SQ were: 34.7% depressed, 45% diagnosed, 55.3% treated and 33% of treated achieving remission. Compared to PWH without depression, we assumed the probability of being non-virally suppressed increased by 1.57 times for PWH with depression (PWH-D), and by 0.95 times for PWH with remitted depression. RESULTS: There was an average increase of 14.6% (11.5-18.5) in the proportion of PWH-D who achieved VLS in EDC compared to SQ. Among all PWH, there was a 4.7% (3.4-6.0) increase in the proportion who achieved VLS in EDC compared to SQ. CONCLUSIONS: Fully diagnosing and adequately treating depression would improve health and quality of life for a substantial proportion of PWH-D and result in a nearly 5% increase in expected rates of VLS in the United States, supporting national prevention goals.

We present the Progression and Transmission of HIV (PATH 4.0), a simulation tool for analyses of cluster detection and intervention strategies. Molecular clusters are groups of HIV infections that are genetically similar, indicating rapid HIV transmission where HIV prevention resources are needed to improve health outcomes and prevent new infections. PATH 4.0 was constructed using a newly developed agent-based evolving network modeling (ABENM) technique and evolving contact network algorithm (ECNA) for generating scale-free networks. ABENM and ECNA were developed to facilitate simulation of transmission networks for low-prevalence diseases, such as HIV, which creates computational challenges for current network simulation techniques. Simulating transmission networks is essential for studying network dynamics, including clusters. We validated PATH 4.0 by comparing simulated projections of HIV diagnoses with estimates from the National HIV Surveillance System (NHSS) for 2010-2017. We also applied a cluster generation algorithm to PATH 4.0 to estimate cluster features, including the distribution of persons with diagnosed HIV infection by cluster status and size and the size distribution of clusters. Simulated features matched well with NHSS estimates, which used molecular methods to detect clusters among HIV nucleotide sequences of persons with HIV diagnosed during 2015-2017. Cluster detection and response is a component of the U.S. Ending the HIV Epidemic strategy. While surveillance is critical for detecting clusters, a model in conjunction with surveillance can allow us to refine cluster detection methods, understand factors associated with cluster growth, and assess interventions to inform effective response strategies. As surveillance data are only available for cases that are diagnosed and reported, a model is a critical tool to understand the true size of clusters and assess key questions, such as the relative contributions of clusters to onward transmissions. We believe PATH 4.0 is the first modeling tool available to assess cluster detection and response at the national-level and could help inform the national strategic plan. © 2021 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)

OBJECTIVE: Analyzing HIV care service targets for achieving a national goal of a 25% reduction in annual HIV incidence and evaluating the use of annual HIV diagnoses to measure progress in incidence reduction. DESIGN: Because there are considerable interactions among HIV care services, we model the dynamics of combinations of increases in HIV care continuum targets to identify those that would achieve 25% reductions in annual incidence and diagnoses. METHODS: We used Progression and Transmission of HIV/AIDS (PATH 2.0), an agent-based dynamic stochastic simulation of HIV in the United States. RESULTS: A 25% reduction in annual incidence could be achieved by multiple alternative combinations of percentages of persons with diagnosed infection and persons with viral suppression including 85% and 68%, respectively, and 90% and 59%, respectively. The first combination corresponded to an 18% reduction in annual diagnoses, and infections being diagnosed at a median CD4 count of 372 cells/muL or approximately 3.8 years from time of infection. The corresponding values on the second combination are 4%, 462 cells/muL, and 2.0 years, respectively. CONCLUSIONS: Our analysis provides policy makers with specific targets and alternative choices to achieve the goal of a 25% reduction in HIV incidence. Reducing annual diagnoses does not equate to reducing annual incidence. Instead, progress toward reducing incidence can be measured by monitoring HIV surveillance data trends in CD4 count at diagnosis along with the proportion who have achieved viral suppression to determine where to focus local programmatic efforts.

BACKGROUND: HIV transmission is the result of complex dynamics in the risk behaviors, partnership choices, disease stage and position along the HIV care continuum-individual characteristics that themselves can change over time. Capturing these dynamics and simulating transmissions to understand the chief sources of transmission remain important for prevention. METHODS: The Progression and Transmission of HIV/AIDS (PATH 2.0) is an agent-based model of a sample of 10,000 people living with HIV (PLWH), who represent all men who have sex with men (MSM) and heterosexuals living with HIV in the U.S.A. Persons uninfected were modeled as populations, stratified by risk and gender. The model included detailed individual-level data from several large national surveillance databases. The outcomes focused on average annual transmission rates from 2008 through 2011 by disease stage, HIV care continuum, and sexual risk group. RESULTS: The relative risk of transmission of those in the acute phase was nine-times [5th and 95th percentile simulation interval (SI): 7, 12] that of those in the non-acute phase, although, on average, those with acute infections comprised 1% of all PLWH. The relative risk of transmission was 24- to 50-times as high for those in the non-acute phase who had not achieved viral load suppression as compared with those who had. The relative risk of transmission among MSM was 3.2-times [SI: 2.7, 4.0] that of heterosexuals. Men who have sex with men and women generated 46% of sexually acquired transmissions among heterosexuals. CONCLUSIONS: The model results support a continued focus on early diagnosis, treatment and adherence to ART, with an emphasis on prevention efforts for MSM, a subgroup of whom appear to play a role in transmission to heterosexuals.

BACKGROUND: New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. FINDINGS: In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. INTERPRETATION: Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. FUNDING: Bill & Melinda Gates Foundation, WHO.

BACKGROUND: Chlamydia and gonorrhea infections can lead to serious and costly sequelae in women, but sequelae in men are rare. In accordance with the Centers for Disease Control and Prevention guidelines, female jail inmates in Maricopa County (Phoenix area), Arizona, are screened for these infections. Owing to lack of evidence of screening benefits in men, male inmates are tested and treated based on symptoms only. METHODS: We developed a probabilistic simulation model to simulate chlamydia and gonorrhea infections in Maricopa County jail male inmates and transmissions to female partners per year. We estimated the cost-effectiveness of screening as the cost per infection averted. Costs were estimated from the perspective of the Maricopa County Department of Public Health and the Correctional Health Services. RESULTS: Compared with symptom-based testing and treating strategy, screening male arrestees of all ages and only those 35 years or younger yielded the following results: averted approximately 556 and 491 cases of infection in women at a cost of approximately US $1240 and $860 per case averted, respectively, if screened during physical examination (between days 8 and 14 from entry to jail), and averted approximately 1100 and 995 cases of infections averted at a cost of US $1030 and $710 per infection averted, respectively, if screened early, within 2 to 3 days from entry to jail. CONCLUSIONS: Screening of male inmates incurs a modest cost per infection averted in women compared with symptom-based testing. Screening in correctional settings can be used by public health programs to reduce disease burden, sequelae, and associated costs.

BACKGROUND: Lifetime costs of care and quality of life estimates for human immunodeficiency virus (HIV)-infected persons depend upon the disease stage at which these persons are diagnosed, enter care, and start antiretroviral therapy (ART). Using updated estimates, we analyzed the effect of late versus early diagnosis/entry on U.S. lifetime care costs, quality of life estimates, and HIV transmissions. METHODS: We used the Progression and Transmission of HIV/AIDS (PATH) model to estimate discounted (3%) lifetime treatment costs ($US 2011) and quality of life variables from time of infection for cohorts of 10,000 HIV-infected index patients in four categories of CD4 count (cells/microL) at diagnosis: (I) ≤ 200; (II) 201 - 350; (III) 351 - 500 and (IV) 501 - 900. We assumed index patient diagnoses were uniformly distributed across the CD4 count range in each category and that patients entered care at the time of diagnosis, remained in care, and were eligible to initiate ART at a CD4 count of 500 cells/microL. We also estimated lifetime transmissions of the index patients. RESULTS: Discounted average lifetime costs varied from $253,000 for category (I) index patients to $402,000 for category (IV) patients. Discounted quality-adjusted life years lost decreased from 7.95 to 4.45 across these categories, additional years of life expectancy increased from 30.8 to 38.1, and lifetime transmissions decreased from 1.40 to 0.72. CONCLUSIONS: Early diagnosis and treatment of HIV infection increases lifetime costs but improves length and quality of life and reduces by nearly 50% the number of new infections transmitted.

BACKGROUND: One of the goals of the National HIV/AIDS Strategy (NHAS) is to increase the proportion of HIV-infected individuals linked to care within 3 months of diagnosis (early linkage) from 65% to 85%. Earlier access to care, and eventually, to treatment, increases life-expectancy and quality of life for HIV-infected persons. However, longer treatment is also associated with higher costs, especially for antiretroviral drugs. We evaluated the cost-effectiveness of achieving the NHAS goal and estimated the maximum cost that HIV programs could spend on linkage to care and remain cost-effective. METHODS: We used the Progression and Transmission of HIV/AIDS (PATH) model to estimate the effects on life-measures and costs associated with increasing early linkage to care from 65% to 85%. We estimated an incremental cost-effectiveness ratio as the additional cost required to reach the target divided by the quality-adjusted life-years (QALYs) gained and assumed that programs costing $100,000 or less per QALY gained are cost-effective. RESULTS: Achieving the NHAS linkage-to-care goal increased life expectancy by 0.4 years and delayed the onset of AIDS by 1.2 years on average for every HIV-diagnosed person. Increasing early linkage to care cost an extra $62,200 per quality-adjusted life-year gained, considering only benefits to index persons. The maximum that could be cost-effectively spent on early linkage-to-care interventions was approximately $ 5,100 per HIV-diagnosed person. CONCLUSION: Considerable investment can be cost-effectively made to achieve the NHAS goal on early linkage to care.