Efficient estimation of human immunodeficiency virus incidence rate using a pooled cross-sectional cohort study design.

Development of methods to accurately estimate human immunodeficiency virus (HIV) incidence rate remains a challenge. Ideally, one would follow a random sample of HIV-negative individuals under a longitudinal study design and identify incident cases as they arise. Such designs can be prohibitively resource intensive and therefore alternative designs may be preferable. We propose such a simple, less resource-intensive study design and develop a weighted log likelihood approach which simultaneously accounts for selection bias and outcome misclassification error. The design is based on a cross-sectional survey which queries individuals' time since last HIV-negative test, validates their test results with formal documentation whenever possible, and tests all persons who do not have documentation of being HIV-positive. To gain efficiency, we update the weighted log likelihood function with potentially misclassified self-reports from individuals who could not produce documentation of a prior HIV-negative test and investigate large sample properties of validated sub-sample only versus pooled sample estimators through extensive Monte Carlo simulations. We illustrate our method by estimating incidence rate for individuals who tested HIV-negative within 1.5 and 5 years prior to Botswana Combination Prevention Project enrolment. This article establishes that accurate estimates of HIV incidence rate can be obtained from individuals' history of testing in a cross-sectional cohort study design by appropriately accounting for selection bias and misclassification error. Moreover, this approach is notably less resource-intensive compared to longitudinal and laboratory-based methods.

Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie/BCPP): a cluster-randomised trial.

BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana.

BACKGROUND: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown. METHODS: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals. RESULTS: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35). CONCLUSIONS: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).

Short Communication: Viral Genetic Linkage Analysis Among Black Men Who Have Sex With Men (HIV Prevention Trials Network 061).

Analysis of viral genetic linkage can reveal generalized transmission patterns within a population. The HIV Prevention Trials Network 061 study evaluated HIV incidence among black men who have sex with men. HIV genotypes from 169 men who were HIV infected at enrollment and 23 men who seroconverted during the study were analyzed for genetic linkage. This analysis showed some associations of viral linkage with income, study site, and timing of infection.

Estimating mono- and bi-phasic regression parameters using a mixture piecewise linear Bayesian hierarchical model.

The dynamics of tumor burden, secreted proteins or other biomarkers over time, is often used to evaluate the effectiveness of therapy and to predict outcomes for patients. Many methods have been proposed to investigate longitudinal trends to better characterize patients and to understand disease progression. However, most approaches assume a homogeneous patient population and a uniform response trajectory over time and across patients. Here, we present a mixture piecewise linear Bayesian hierarchical model, which takes into account both population heterogeneity and nonlinear relationships between biomarkers and time. Simulation results show that our method was able to classify subjects according to their patterns of treatment response with greater than 80% accuracy in the three scenarios tested. We then applied our model to a large randomized controlled phase III clinical trial of multiple myeloma patients. Analysis results suggest that the longitudinal tumor burden trajectories in multiple myeloma patients are heterogeneous and nonlinear, even among patients assigned to the same treatment cohort. In addition, between cohorts, there are distinct differences in terms of the regression parameters and the distributions among categories in the mixture. Those results imply that longitudinal data from clinical trials may harbor unobserved subgroups and nonlinear relationships; accounting for both may be important for analyzing longitudinal data.

Using a network-based approach and targeted maximum likelihood estimation to evaluate the effect of adding pre-exposure prophylaxis to an ongoing test-and-treat trial.

BACKGROUND: Several cluster-randomized trials are underway to investigate the implementation and effectiveness of a universal test-and-treat strategy on the HIV epidemic in sub-Saharan Africa. We consider nesting studies of pre-exposure prophylaxis within these trials. Pre-exposure prophylaxis is a general strategy where high-risk HIV- persons take antiretrovirals daily to reduce their risk of infection from exposure to HIV. We address how to target pre-exposure prophylaxis to high-risk groups and how to maximize power to detect the individual and combined effects of universal test-and-treat and pre-exposure prophylaxis strategies. METHODS: We simulated 1000 trials, each consisting of 32 villages with 200 individuals per village. At baseline, we randomized the universal test-and-treat strategy. Then, after 3 years of follow-up, we considered four strategies for targeting pre-exposure prophylaxis: (1) all HIV- individuals who self-identify as high risk, (2) all HIV- individuals who are identified by their HIV+ partner (serodiscordant couples), (3) highly connected HIV- individuals, and (4) the HIV- contacts of a newly diagnosed HIV+ individual (a ring-based strategy). We explored two possible trial designs, and all villages were followed for a total of 7 years. For each village in a trial, we used a stochastic block model to generate bipartite (male-female) networks and simulated an agent-based epidemic process on these networks. We estimated the individual and combined intervention effects with a novel targeted maximum likelihood estimator, which used cross-validation to data-adaptively select from a pre-specified library the candidate estimator that maximized the efficiency of the analysis. RESULTS: The universal test-and-treat strategy reduced the 3-year cumulative HIV incidence by 4.0% on average. The impact of each pre-exposure prophylaxis strategy on the 4-year cumulative HIV incidence varied by the coverage of the universal test-and-treat strategy with lower coverage resulting in a larger impact of pre-exposure prophylaxis. Offering pre-exposure prophylaxis to serodiscordant couples resulted in the largest reductions in HIV incidence (2% reduction), and the ring-based strategy had little impact (0% reduction). The joint effect was larger than either individual effect with reductions in the 7-year incidence ranging from 4.5% to 8.8%. Targeted maximum likelihood estimation, data-adaptively adjusting for baseline covariates, substantially improved power over the unadjusted analysis, while maintaining nominal confidence interval coverage. CONCLUSION: Our simulation study suggests that nesting a pre-exposure prophylaxis study within an ongoing trial can lead to combined intervention effects greater than those of universal test-and-treat alone and can provide information about the efficacy of pre-exposure prophylaxis in the presence of high coverage of treatment for HIV+ persons.

Can the Heterosexual HIV Epidemic be Eliminated in South Africa Using Combination Prevention? A Modeling Analysis.

Little is known about how combining efficacious interventions for human immunodeficiency virus (HIV) prevention could lead to HIV elimination. We used an agent-based simulation model, the HIV calibrated dynamic model, to assess the potential for HIV elimination in South Africa. We examined several scenarios (from continuation of the current status quo to perfect achievement of targets) with differing combinations of male condom use, adult male circumcision, HIV testing, and early antiretroviral therapy (ART). We varied numerous parameters, including the proportion of adult males circumcised, the frequency of condom use during sex acts, acceptance of HIV testing, linkage to health care, criteria for ART initiation, ART viral suppression rates, and loss to follow-up. Maintaining current levels of combination prevention would lead to increasing HIV incidence and prevalence in South Africa, while the perfect combination scenario was projected to eliminate HIV on a 50-year time scale from 2013 to 2063. Perfecting testing and treatment, without changing condom use or circumcision rates, resulted in an 89% reduction in HIV incidence but not elimination. Universal adult male circumcision alone resulted in a 21% incidence reduction within 20 years. Substantial decreases in HIV incidence are possible from sufficient uptake of both primary prevention and ART, but with continuation of the status quo, HIV elimination in South Africa is unlikely within a 50-year time scale.

Importance of Viral Sequence Length and Number of Variable and Informative Sites in Analysis of HIV Clustering.

To improve the methodology of HIV cluster analysis, we addressed how analysis of HIV clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering and tree certainty was compared between 401 HIV-1C near full-length genome sequences and subgenomic regions retrieved from the LANL HIV Database. Sliding window analysis was based on 99 windows of 1,000 bp and 45 windows of 2,000 bp. Potential associations between the extent of HIV clustering and sequence length and the number of variable and informative sites were evaluated. The near full-length genome HIV sequences showed the highest extent of HIV clustering and the highest tree certainty. At the bootstrap threshold of 0.80 in maximum likelihood (ML) analysis, 58.9% of near full-length HIV-1C sequences but only 15.5% of partial pol sequences (ViroSeq) were found in clusters. Among HIV-1 structural genes, pol showed the highest extent of clustering (38.9% at a bootstrap threshold of 0.80), although it was significantly lower than in the near full-length genome sequences. The extent of HIV clustering was significantly higher for sliding windows of 2,000 bp than 1,000 bp. We found a strong association between the sequence length and proportion of HIV sequences in clusters, and a moderate association between the number of variable and informative sites and the proportion of HIV sequences in clusters. In HIV cluster analysis, the extent of detectable HIV clustering is directly associated with the length of viral sequences used, as well as the number of variable and informative sites. Near full-length genome sequences could provide the most informative HIV cluster analysis. Selected subgenomic regions with a high extent of HIV clustering and high tree certainty could also be considered as a second choice.

HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients.

OBJECTIVES: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury. METHODS: We enrolled 61 cART-naïve HIV-infected Thais in a prospective study and measured HIV DNA in CD14(+) enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF). RESULTS: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log10 plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log10 CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p = 0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions. INTERPRETATION: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naïve HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.

Antiretroviral monocyte efficacy score linked to cognitive impairment in HIV.

BACKGROUND: Monocytes transmigrating to the brain play a central role in HIV neuropathology. We hypothesized that the continued existence of neurocognitive impairment (NCI) despite potent antiretroviral (ARV) therapy is mediated by the inability of such therapy to control this monocyte/macrophage reservoir. METHODS: Cross-sectional and longitudinal analyses were conducted within a prospectively enrolled cohort. We devised a monocyte efficacy (ME) score based on the anticipated effectiveness of ARV medications against monocytes/macrophages using published macrophage in vitro drug efficacy data. We examined, within an HIV neurocognitive database, its association with composite neuropsychological test scores (NPZ8) and clinical cognitive diagnoses among subjects on stable ARV medications unchanged for >6 months prior to assessment. RESULTS: Among 139 subjects on ARV therapy, higher ME score correlated with better NPZ8 performance (r=0.23, P<0.01), whereas a score devised to quantify expected penetration effectiveness of ARVs into the brain (CPE score) did not (r=0.12, P=0.15). In an adjusted model (adjusted r(2)=0.12), ME score (ß=0.003, P=0.02), CD4(+) T-cell nadir (ß=0.001, P<0.01) and gender (ß=-0.456, P=0.02) were associated with NPZ8, whereas CPE score was not (ß=0.003, P=0.94). A higher ME score was associated with better clinical cognitive status (P<0.01). With a range of 12.5-433.0 units, a 100-unit increase in ME score resulted in a 10.6-fold decrease in the odds of a dementia diagnosis compared with normal cognition (P=0.01). CONCLUSIONS: ARV efficacy against monocytes/macrophages correlates with cognitive function in HIV-infected individuals on ARV therapy within this cohort. If validated, efficacy against monocytes/macrophages may provide a new target to improve HIV NCI.

Can computer-based feedback improve emergency department patient uptake of rapid HIV screening?

OBJECTIVE: We determine whether (1) an audiocomputer-delivered tailored feedback intervention increases emergency department (ED) patient uptake of opt-in, nontargeted rapid HIV screening; and (2) uptake is greater among patients who report more HIV risk and among those whose self-perceived HIV risk increases from baseline after completion of an HIV risk assessment. METHODS: ED patients aged 18 to 64 years were randomly assigned to receive either an assessment about reported and self-perceived HIV risk or an identical assessment plus feedback about their risk for having or acquiring an HIV infection, tailored according to their reported risk. All participants were offered a fingerstick rapid HIV test. Two-sample tests of binomial proportions were used to compare screening uptake by study arm. Multivariable logistic regression was used to assess the relationship of reported HIV risk and an increase in self-perceived HIV risk with uptake of HIV screening. RESULTS: Of the 566 participants, the median age was 29 years, 62.2% were women, and 66.9% previously had been tested for HIV. Uptake of HIV screening was similar in the intervention and no intervention arms (54.1% versus 55.5% [Δ=-0.01%; 95% confidence interval {CI} -0.09% to 0.07%]). An increase in self-perceived HIV risk predicted greater uptake of HIV screening for women (odds ratio 2.15; 95% CI 1.08 to 4.28) but not men (odds ratio 1.61; 95% CI 0.60 to 4.30). Uptake of HIV screening was not related to reported HIV risk. CONCLUSION: Uptake of rapid HIV screening in the ED was not improved by this feedback intervention. Other methods need to be investigated to improve uptake of HIV screening by ED patients.

Implications of HIV PrEP trials results.

Abstract Six randomized clinical trials have been implemented to examine the efficacy of tenofovir disoproxil fumarate (TDF) and/or TDF/emtricitabine (TDF/FTC) as preexposure prophylaxis for HIV-1 infection (PrEP). Although largely complementary, the six trials have many similar features. As the earliest results become available, an urgent question may arise regarding whether changes should be made in the conduct of the other trials. To consider this in advance, a Consultation on the Implications of HIV Pre-Exposure Prophylaxis (PrEP) Trials Results sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation (BMGF) was held on January 29, 2010, at the Natcher Conference Center, NIH, Bethesda, MD. Participants included basic scientists, clinical researchers (including investigators performing the current PrEP trials), and representatives from the U.S. Food and Drug Administration (FDA) and the agencies sponsoring the trials: the U.S. Centers for Disease Control and Prevention (CDC), the U.S. Agency for International Development (USAID), the BMGF, and the U.S. NIH. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.

HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1-4.2 log(10)) and cART-initiating cohorts (5.1-5.3 log(10)) by about one log(10). The proportion of individuals with high (> or = 50,000 (4.7 log(10)) copies/ml) HIV-1 RNA levels ranged from 24%-28% in the general HIV-positive population cohorts to 65%-83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%-50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load > or = 50,000 (4.7 log(10)) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%-82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified "test-and-treat" strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.

The relationship of reported HIV risk and history of HIV testing among emergency department patients.

OBJECTIVE: Among a random sample of emergency department (ED) patients, we sought to determine the extent to which reported risk for human immunodeficiency virus (HIV) is related to ever having been tested for HIV. METHODS: A random sample of patients (aged 18-64 years) from an adult, urban, northeastern United States, academic ED were surveyed about their history of ever having been tested for HIV and their reported HIV risk behaviors. A reported HIV risk score was calculated from the survey responses and divided into 4 levels, based on quartiles of the risk scores. Pearson's X(2) testing was used to compare HIV testing history and level of reported HIV risk. Logistic regression models were created to investigate the association between level of reported HIV risk and the outcome of ever having been tested for HIV. RESULTS: Of the 557 participants, 62.1% were female. A larger proportion of females than males (71.4% vs 60.6%; P < 0.01) reported they had been tested for HIV. Among the 211 males, 11.4% reported no HIV risk, and among the 346 females, 10.7% reported no HIV risk. The proportion of those who had been tested for HIV was greater among those reporting any risk compared with those reporting no risk for females (75.4% vs 37.8%; P < 0.001), but not for males (59.9% vs 66.7%; P < 0.52). However, certain high-risk behaviors, such as a history of injection-drug use, were associated with prior HIV testing for both genders. In the logistic regression analyses, there was no relationship between increasing level of reported HIV risk and a history of ever having been tested for HIV for males. For females, a history of ever having been tested was related to increasing level of reported risk, but not in a linear fashion. CONCLUSIONS: The relationship between reported HIV risk and history of testing among these ED patients was complex and differed by gender. Among these patients, having greater risk did not necessarily mean a higher likelihood of ever having been tested for HIV.

Demographic variations in HIV testing history among emergency department patients: implications for HIV screening in US emergency departments.

OBJECTIVE: To determine the proportion of emergency department (ED) patients who have been tested for human immunodeficiency virus (HIV) infection and assess if patient history of HIV testing varies according to patient demographic characteristics. DESIGN: From July 2005-July 2006, a random sample of 18-55-year-old English-speaking patients being treated for sub-critical injury or illness at a northeastern US ED were interviewed on their history of HIV testing. Logistic regression models were created to compare patients by their history of being tested for HIV according to their demography. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Of 2107 patients surveyed who were not known to be HIV-infected, the median age was 32 years; 54% were male, 71% were white, and 45% were single/never married; 49% had private health-care insurance and 45% had never been tested for HIV. Of the 946 never previously tested for HIV, 56.1% did not consider themselves at risk for HIV. In multivariable logistic regression analyses, those less likely to have been HIV tested were male (OR: 1.32 [1.37-2.73]), white (OR: 1.93 [1.37-2.73]), married (OR: 1.53 [1.12-2.08]), and had private health-care insurance (OR: 2.10 [1.69-2.61]). There was a U-shaped relationship between age and history of being tested for HIV; younger and older patients were less likely to have been tested. History of HIV testing and years of formal education were not related. CONCLUSION: Almost half of ED patients surveyed had never been tested for HIV. Certain demographic groups are being missed though HIV diagnostic testing and screening programmes in other settings. These groups could potentially be reached through universal screening.

Emergency department patient perceptions and preferences on opt-in rapid HIV screening program components.

The aim of this investigation was to assess emergency department (ED) patients' perceptions and preferences about an opt-in, universal, rapid HIV screening program and identify patient groups who expressed stronger beliefs about components of the testing program. From July 2005 to July 2006, ED patients in the opt-in, universal, rapid HIV screening program were interviewed in person. Multivariable regression models were used to compare participants on their beliefs about the program components. Of the 561 participants, 62.0% had previously been tested for HIV. The majority of participants (58.8%) believed the rapid and standard/conventional HIV tests to be equally accurate, 27.7% believed the rapid test to be less or much less accurate, and 8.7% believed the rapid test to be more or much more accurate. Almost two-thirds (65.1%) favored having a rapid instead of a standard/conventional HIV test, 94.6% wanted the test results within one hour, and 61.3% would be likely or very likely to undergo testing in the ED if it prolonged their ED visit. Almost all (92.5%) believed that their medical care was "not at all" delayed because of being tested, 94.1% believed that testing did "not at all" divert attention from the reason for their ED visit, and 80.9% thought that testing in the ED was "not at all" stressful. In multivariable logistic regression models, males and those with more than 12 years of formal education showed greater concerns about the rapid HIV test's accuracy. Hispanic/Latinos, participants with governmental insurance, and those previously HIV tested were more apt to be screened for HIV even if testing delayed their ED departure. Overall, participants were highly accepting of the components of this opt-in rapid HIV screening program. However, concerns regarding the accuracy of the rapid HIV test might limit test acceptance and should be addressed during pre-test information procedures.

Video as an effective method to deliver pretest information for rapid human immunodeficiency testing.

OBJECTIVES: Video-based delivery of human immunodeficiency virus (HIV) pretest information might assist in streamlining HIV screening and testing efforts in the emergency department (ED). The objectives of this study were to determine if the video "Do you know about rapid HIV testing?" is an acceptable alternative to an in-person information session on rapid HIV pretest information, in regard to comprehension of rapid HIV pretest fundamentals, and to identify patients who might have difficulties in comprehending pretest information. METHODS: This was a noninferiority trial of 574 participants in an ED opt-in rapid HIV screening program who were randomly assigned to receive identical pretest information from either an animated and live-action 9.5-minute video or an in-person information session. Pretest information comprehension was assessed using a questionnaire. The video would be accepted as not inferior to the in-person information session if the 95% confidence interval (CI) of the difference (Delta) in mean scores on the questionnaire between the two information groups was less than a 10% decrease in the in-person information session arm's mean score. Linear regression models were constructed to identify patients with lower mean scores based upon study arm assignment, demographic characteristics, and history of prior HIV testing. RESULTS: The questionnaire mean scores were 20.1 (95% CI = 19.7 to 20.5) for the video arm and 20.8 (95% CI = 20.4 to 21.2) for the in-person information session arm. The difference in mean scores compared to the mean score for the in-person information session met the noninferiority criterion for this investigation (Delta = 0.68; 95% CI = 0.18 to 1.26). In a multivariable linear regression model, Blacks/African Americans, Hispanics, and those with Medicare and Medicaid insurance exhibited slightly lower mean scores, regardless of the pretest information delivery format. There was a strong relationship between fewer years of formal education and lower mean scores on the questionnaire. Age, gender, type of insurance, partner/marital status, and history of prior HIV testing were not predictive of scores on the questionnaire. CONCLUSIONS: In terms of patient comprehension of rapid HIV pretest information fundamentals, the video was an acceptable substitute to pretest information delivered by an HIV test counselor. Both the video and the in-person information session were less effective in providing pretest information for patients with fewer years of formal education.

Effectiveness of increasing emergency department patients' self-perceived risk for being human immunodeficiency virus (HIV) infected through audio computer self-interview-based feedback about reported HIV risk behaviors.

OBJECTIVES: Prior research has demonstrated that emergency department (ED) patient acceptance of human immunodeficiency virus (HIV) screening is partially dependent on patients' self-perceived risk of infection. The primary objective of this study was to determine the effectiveness of audio computer-assisted self-interview (ACASI)-based feedback. The intervention aimed to increase patient's self-perceived risk of being HIV infected by providing immediate feedback on their risk behaviors. METHODS: This 1-year, randomized, controlled trial at a U.S. ED enrolled a random sample of 18- to 64-year-old subcritically ill or injured adult patients who were not known to be HIV infected. All participants completed an anonymous, ACASI-based questionnaire about their HIV risk behaviors related to injection drug use and sex, as well as their self-perceived risk for being HIV infected. Participants were randomly assigned to one of two study groups: an intervention group in which participants received immediate ACASI-based feedback in response to each of their reported risk behaviors or a no-intervention group without feedback. Participants were asked to indicate their level of HIV risk on a five-point scale before and after they answered the questions. Change in level of self-perceived HIV risk was calculated and compared by study group using Pearson's chi-square test. An HIV risk behavior score that summarized reported HIV risk behavior was devised. Because HIV risk behaviors differ by sex, scores were calculated separately for each sex. Linear regression models that adjusted for study group and same subject covariance were employed to determine if higher HIV risk behavior scores were associated with an increase in self-perceived HIV risk. RESULTS: Of the 566 trial participants, the median age was 29 years (interquartile range [IQR] = 22-43 years), 62.2% were females, and 66.9% had been tested previously for HIV. After answering the reported HIV risk behavior questions, 12.6% of participants had an increase, 79.9% had no change, and 7.5% had a decrease in self-perceived HIV risk. Of the 46.6% of participants who initially indicated that they were not at risk for HIV, 11.4% had an increase in self-perceived HIV risk after answering the reported HIV risk behavior questions. Change in self-perceived HIV risk did not differ by study group (p = 0.77). There were no differences in reported HIV risk scores between the intervention and no-intervention groups for females (p = 0.78) or males (p = 0.86). In the linear regression models, a greater increase in self-perceived HIV risk was associated with higher reported HIV risk behavior scores for females (beta = 0.59, 95% confidence interval [CI] = 0.15, 1.04) but not for males (beta = 1.00, 95% CI = -0.13 to 2.14). CONCLUSIONS: Some ED patients can be moved, although modestly, to recognize their risk for being HIV infected by asking about their HIV risk behaviors. However, ACASI-based feedback messages about HIV risk behaviors do not increase subjects' self-perceived HIV risk. Female ED patients appear to increase their self-perceived HIV risk more than males when queried about their HIV risk behaviors.

Accommodating uncertainty in a tree set for function estimation.

Multiple branching trees have been used to model the acquisition of HIV drug resistance mutations, and several different algorithms have been developed to construct the tree set that best describes the data. These algorithms have mainly focused on the structure of the tree set. The focal point of this paper is estimation of functions of the tree set parameters that incorporate uncertainty in the tree set. The functions of interest are the state probabilities, the co-occurrence of mutations and the order of acquisition. Such functions are of interest because they help characterize the genetic pathways that lead to multi-drug resistance. We propose a bootstrap technique to account for the additional variability in estimates due to uncertainty in the tree set. The methods are applied to genetic sequences of patients from a database compiled by the Forum for Collaborative HIV Research in an effort to characterize genetic pathways to resistance to drugs from the nucleoside reverse transcriptase inhibitor (NRTI) class. The main results were that patients with a 211K mutation in the RT region of the viral genome were more likely to have a 215Y mutation and less likely to have a 70R mutation compared to patients without a 211K mutation.