Potential for community based surveillance of febrile diseases: Feasibility of self-administered rapid diagnostic tests in Iquitos, Peru and Phnom Penh, Cambodia.

Rapid diagnostic tests (RDTs) have the potential to identify infectious diseases quickly, minimize disease transmission, and could complement and improve surveillance and control of infectious and vector-borne diseases during outbreaks. The U.S. Defense Threat Reduction Agency's Joint Science and Technology Office (DTRA-JSTO) program set out to develop novel point-of-need RDTs for infectious diseases and deploy them for home use with no training. The aim of this formative study was to address two questions: 1) could community members in Iquitos, Peru and Phnom Penh, Cambodia competently use RDTs of different levels of complexity at home with visually based instructions provided, and 2) if an RDT were provided at no cost, would it be used at home if family members displayed febrile symptoms? Test kits with written and video (Peru only) instructions were provided to community members (Peru [n = 202]; Cambodia [n = 50]) or community health workers (Cambodia [n = 45]), and trained observers evaluated the competency level for each of the several steps required to successfully operate one of two multiplex RDTs on themselves or other consenting participant (i.e., family member). In Iquitos, >80% of residents were able to perform 11/12 steps and 7/15 steps for the two- and five-pathogen test, respectively. Competency in Phnom Penh never reached 80% for any of the 12 or 15 steps for either test; the percentage of participants able to perform a step ranged from 26-76% and 23-72%, for the two- and five-pathogen tests, respectively. Commercially available NS1 dengue rapid tests were distributed, at no cost, to households with confirmed exposure to dengue or Zika virus; of 14 febrile cases reported, six used the provided RDT. Our findings support the need for further implementation research on the appropriate level of instructions or training needed for diverse devices in different settings, as well as how to best integrate RDTs into existing local public health and disease surveillance programs at a large scale.

Potential Use of Community-Based Rapid Diagnostic Tests for Febrile Illnesses: Formative Research in Peru and Cambodia.

In 2012, the U.S. Defense Threat Reduction Agency Joint Science and Technology Office initiated a program to develop novel point-of-need diagnostic devices for surveillance of emerging infectious diseases including dengue, malaria, plague, and melioidosis. Prior to distribution of devices to observe their correct use among community members in Iquitos, Peru, and Phnom Penh, Cambodia, research was conducted to: 1) assess acceptability of use, including the motivation to use a rapid diagnostic test (RDT) before or instead of seeking care at a health facility, 2) explore comprehension of RDT use instructions, and 3) examine possible strategies for large scale RDT distribution and use at each site. In February 2014, 9 focus group discussions (FGD) with community members and 5 FGD with health professionals were conducted in Iquitos, and 9 FGD with community members and 9 in-depth interviews with health professionals in Phnom Penh. In both places, participants agreed to use the device themselves (involving finger prick) or could identify someone who could do so in their home or neighborhood. The main incentive to RDT use in both sites was the ability for device results to be used for care facilitation (post confirmatory tests), specifically reduced wait times to be seen or obtain a diagnosis. Comprehension of RDT use instructions was assessed in Iquitos by asking some participants to apply the device to research team members; after watching a short video, most steps were done correctly. In Phnom Penh, participants were asked to describe each step after reading the instructions; they struggled with comprehension. Health professionals' main concerns in both sites were their community's ability to accurately use the test, handle complicated instructions, and safety (i.e., disposal of lancets). Health system structure and ability to use home diagnostic devices varied in the two disease endemic sites, with substantial challenges in each, suggesting the need for different strategies for RDT large scale community use, and illustrating the value of formative research before deployment of novel technologies.

Development of an Agent-Based Model to Investigate the Impact of HIV Self-Testing Programs on Men Who Have Sex With Men in Atlanta and Seattle.

BACKGROUND: In the United States HIV epidemic, men who have sex with men (MSM) remain the most profoundly affected group. Prevention science is increasingly being organized around HIV testing as a launch point into an HIV prevention continuum for MSM who are not living with HIV and into an HIV care continuum for MSM who are living with HIV. An increasing HIV testing frequency among MSM might decrease future HIV infections by linking men who are living with HIV to antiretroviral care, resulting in viral suppression. Distributing HIV self-test (HIVST) kits is a strategy aimed at increasing HIV testing. Our previous modeling work suggests that the impact of HIV self-tests on transmission dynamics will depend not only on the frequency of tests and testers' behaviors but also on the epidemiological and testing characteristics of the population. OBJECTIVE: The objective of our study was to develop an agent-based model to inform public health strategies for promoting safe and effective HIV self-tests to decrease the HIV incidence among MSM in Atlanta, GA, and Seattle, WA, cities representing profoundly different epidemiological settings. METHODS: We adapted and extended a network- and agent-based stochastic simulation model of HIV transmission dynamics that was developed and parameterized to investigate racial disparities in HIV prevalence among MSM in Atlanta. The extension comprised several activities: adding a new set of model parameters for Seattle MSM; adding new parameters for tester types (ie, regular, risk-based, opportunistic-only, or never testers); adding parameters for simplified pre-exposure prophylaxis uptake following negative results for HIV tests; and developing a conceptual framework for the ways in which the provision of HIV self-tests might change testing behaviors. We derived city-specific parameters from previous cohort and cross-sectional studies on MSM in Atlanta and Seattle. Each simulated population comprised 10,000 MSM and targeted HIV prevalences are equivalent to 28% and 11% in Atlanta and Seattle, respectively. RESULTS: Previous studies provided sufficient data to estimate the model parameters representing nuanced HIV testing patterns and HIV self-test distribution. We calibrated the models to simulate the epidemics representing Atlanta and Seattle, including matching the expected stable HIV prevalence. The revised model facilitated the estimation of changes in 10-year HIV incidence based on counterfactual scenarios of HIV self-test distribution strategies and their impact on testing behaviors. CONCLUSIONS: We demonstrated that the extension of an existing agent-based HIV transmission model was sufficient to simulate the HIV epidemics among MSM in Atlanta and Seattle, to accommodate a more nuanced depiction of HIV testing behaviors than previous models, and to serve as a platform to investigate how HIV self-tests might impact testing and HIV transmission patterns among MSM in Atlanta and Seattle. In our future studies, we will use the model to test how different HIV self-test distribution strategies might affect HIV incidence among MSM.

Improving Estimation of HIV Viral Suppression in the United States: A Method to Adjust HIV Surveillance Estimates From the Medical Monitoring Project Using Cohort Data.

The US Centers for Disease Control and Prevention has estimated human immunodeficiency virus (HIV) viral suppression (VS) using 2 data sources. The National HIV Surveillance System estimate (50% of HIV-diagnosed persons in 2012) is derived from viral load reporting from a subset of jurisdictions that vary yearly. The Medical Monitoring Project (MMP) estimate (42% of HIV-diagnosed persons in 2012) is based on a sample of persons receiving HIV care during the first 4 months of each year. We developed the cohort-adjustment method to reconstruct VS estimates, accounting for persons receiving care later in the year. Using the HIV Outpatient Study cohort, we assessed timing of care receipt, demographics, and VS at last test (<200 vs. ≥200 copies/mL), standardizing MMP to HIV Outpatient Study data using multivariable regression models and yielding adjusted VS estimates. We estimated that 52% (95% CI: 48, 56) of HIV-diagnosed persons achieved VS in 2012. Differences from previously published estimates were due to: 1) 23% underestimation of persons receiving HIV care, and 2) lower VS rates among persons receiving care outside versus inside the 4-month MMP sampling period (79% vs. 88%). This methodology yielded VS estimates closer to the National HIV Surveillance System estimate than previously published. Use of more, geographically diverse cohort data may enable assessment of temporal trends.

HIV Risk Behaviors and Utilization of Prevention Services, Urban and Rural Men Who Have Sex with Men in the United States: Results from a National Online Survey.

Rural men who have sex with men (MSM) are heavily affected by HIV, and many lack culturally competent HIV prevention resources. Rural MSM may find sexual partners on the internet, which may also be a way to deliver prevention services to them. To understand the differences between rural and urban MSM with respect to HIV risk factors and behaviors and the utilization of online HIV prevention services, we used data from the 2012 Web-Based HIV Behavioral Survey (WHBS). Using WHBS data collected between June and August 2012, we compared the characteristics of MSM with positive or unknown HIV infection status who had sex with a male in the past 12 months, from rural vs urban areas using Chi square tests and median tests. We used logistic regression and calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) to compare self-reported HIV risk behaviors, HIV/STI testing behaviors, use of prevention services, and perceived discrimination. Of the 8166 MSM included in our analysis, 3583 (44%) were from rural areas, and 4583 (56%) were from urban areas. Compared to urban MSM, rural MSM were less likely to ever test for HIV (aPR = 0.94, CI 0.92-0.95), to be tested for HIV in the last year (aPR = 0.83, CI 0.79-0.87), or to receive free condoms (aPR = 0.83, CI 0.79-0.86) or individual prevention counseling in the past year (aPR = 0.86, CI 0.78-0.95). Rural MSM were less likely to have been tested in the last year for syphilis, gonorrhea, or chlamydia (aPR = 0.70, CI 0.62-0.78; aPR = 0.72, CI 0.64-0.81; aPR = 0.75, CI 0.67-0.85, respectively). Rural MSM also reported perceiving less tolerance of gays and bisexuals within their community (aPR = 0.80, CI 0.77-0.84). HIV prevalence is lower among MSM in rural areas compared to MSM in urban areas, but rural MSM report that they are more likely to face intolerance and are less likely to use basic HIV prevention services compared to urban MSM. Therefore, this hard-to-reach population could benefit from prevention services offered through the internet.

Correction: Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men.

[This corrects the article DOI: 10.1371/journal.pone.0178170.].

Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men.

INTRODUCTION: Men who have sex with men (MSM) are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP) is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood. METHODS: We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY) gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1) the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs); and 2) PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds. RESULTS: When PrEP drug costs were reduced by 60% (with no sexual disinhibition) to 80% (assuming 25% sexual disinhibition), PrEP was cost-effective (at <$100,000 per QALY averted) in all scenarios of base-case or better adherence, as long as the background HIV prevalence was greater than 10%. For PrEP to be cost saving at base-case adherence/efficacy levels and at a background prevalence of 20%, drug cost would need to be reduced to $8,021 per year with no disinhibition, and to $2,548 with disinhibition. CONCLUSION: Results from our analysis suggest that PrEP drug costs need to be reduced in order to be cost-effective across a range of background HIV prevalence. Moreover, our results provide guidance on the pricing of generic emtricitabine/tenofovir disoproxil fumarate, in order to provide those at high risk for HIV an affordable prevention option without financial burden on individuals or jurisdictions scaling-up coverage.

Risk Factors Associated With Repeated HIV Testing Among Internet-Using Men Who Have Sex With Men.

Men who have sex with men (MSM) represent a disproportionately impacted risk group for HIV incidence among at-risk U.S. POPULATIONS: Few studies have identified risk factors associated with HIV testing frequency both within and outside of traditional health care settings. MSM enrolled in a prospective cohort were mailed at-home specimen collection kits and followed for a year. Incidence density rate ratios (IDRR) of testing were calculated, and generalized estimating equations were used to analyze the association between HIV testing and behavioral factors. The incidence rate of testing was higher among Black MSM than White MSM (IDRR: 1.3, 95% confidence interval CI [1.1, 1.5]) and higher among MSM who reported 3+ condomless anal intercourse partners (CAI) than MSM who reported no CAI (IDRR: 1.6, 95% CI [1.3, 2.0]). Increasing availability of HIV testing outside traditional health care settings, including at-home testing kits, in conjunction with targeted behavioral interventions and biomedical treatment preventions is needed.

Factors Associated With Condom Breakage During Anal Intercourse: A Cross-Sectional Study of Men Who Have Sex With Men Recruited in an Online Survey.

BACKGROUND: Within the United States, HIV affects men who have sex with men (MSM) disproportionally compared to the general population. In 2011, MSM represented nearly two-thirds of all new HIV infections while representing less than 2% of the US male population. Condoms continue to be the foundation of many HIV prevention programs; however, the failure rate of condoms during anal intercourse among MSM is estimated to be 0.5% to 8%, and condom breakages leave those affected at high risk for HIV transmission. OBJECTIVE: Estimate the frequency of condom breakage and associated demographic and behavioral factors during last act of anal intercourse using data from a national online HIV prevention survey of MSM. METHODS: From March 19 to April 16, 2009, data were collected on 9005 MSM through an online survey of US MSM recruited through a social networking site. Using multivariable logistic regression and controlling for several demographic and sexual risk behaviors, we estimated odds ratios of the association between condom breakage and several risk factors. RESULTS: In the study, 8063 participants reported having at least one male sexual partner in the last 12 months. The median age of participants was 21 years (range 18-65). More than two-thirds (68.2%, 5498/8063) reported anal intercourse during last sex and 16.90% (927/5498) reported using a condom during last anal intercourse act. Condom breakage was reported by 4.4% (28/635) participants who engaged in receptive anal intercourse and 3.5% (16/459) participants who engaged in insertive anal intercourse, with an overall failure rate of 4.0% (95% CI 3.2%-6.0%). Age (adjusted odds ratio [aOR] per 5 years: 0.53 (95% CI 0.30-0.94), number of male sex partners (aOR per 5 sex partners: 1.03 (95% CI 1.00-1.08), and being high or buzzed during sex with a casual sex partner (aOR: 3.14, 95% CI 1.02-9.60) were associated with condom breakage. CONCLUSIONS: Our results indicate condom breakage is an important problem for MSM that may be more common for younger men, for men with more partners, and during sex with casual partners after alcohol consumption or drug use. A better understanding of why condom breakage occurs more often in these groups is needed to improve educational efforts. Further, during this time of expanded interest in new condom designs, consideration should be given to how condom design might minimize breakage during anal sex.

Prevalence, correlates, and outcomes of cryptococcal antigen positivity among patients with AIDS, United States, 1986-2012.

BACKGROUND: Cryptococcal meningitis (CM) is one of the most common causes of AIDS-related mortality worldwide, accounting for 33%-63% of all cases of adult meningitis in sub-Saharan Africa and >500 000 deaths annually. In sub-Saharan Africa, the World Health Organization recommends routinely screening AIDS patients with a CD4 count ≤100 cells/µL for cryptococcal infection. In the United States, there are no recommendations for routine screening. We aimed to determine the prevalence of cryptococcal infection and outcomes of those infected among people living with advanced AIDS in the United States, to inform updates in the prevention and management of CM. METHODS: Using stored sera from participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study from 1986 to 2012, we screened 1872 specimens with CD4 T-cell counts ≤100 cells/µL for cryptococcal antigen (CrAg) using the CrAg lateral flow assay. RESULTS: The overall prevalence of CrAg positivity within the study population was 2.9% (95% confidence interval, .2%-3.8%). Results from multivariable analysis revealed that a previous diagnosis with CM and a CD4 count ≤50 cells/µL were significantly associated with CrAg positivity. Participants who were CrAg positive had significantly shorter survival (2.8 years) than those who were CrAg negative (3.8 years; P = .03). CONCLUSIONS: The prevalence of cryptococcal infection among advanced AIDS patients in the United States was high and above the published cost-effectiveness threshold for routine screening. We recommend routine CrAg screening among human immunodeficiency virus-infected patients with a CD4 count ≤100 cells/µL to detect and treat early infection.

Prevalence and correlates of cryptococcal antigen positivity among AIDS patients--United States, 1986-2012.

Cryptococcal meningitis (CM) is one of the leading opportunistic infections associated with human immunodeficiency virus (HIV) infection. The worldwide burden of CM among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually. The high burden of CM globally comes despite the fact that cryptococcal antigen (CrAg) is detectable weeks before the onset of symptoms, allowing screening for cryptococcal infection and early treatment to prevent CM and CM-related mortality (2). However, few studies have been conducted in the United States to assess the prevalence of cryptococcal infection. To quantify the prevalence of undiagnosed cryptococcal infection in HIV-infected persons in the United States during 1986-2012, stored sera from 1,872 participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study with CD4 T-cell counts <100 cells/µL were screened for CrAg, using the CrAg Lateral Flow Assay (LFA) (Immy, Inc.). This report describes the results of that analysis, which indicated the overall prevalence of CrAg positivity in this population to be 2.9% (95% confidence interval [CI] = 2.2%-3.7%).