HIV policy: the path forward--a joint position paper of the HIV Medicine Association of the Infectious Diseases Society of America and the American College of Physicians.

Executive Summary The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have jointly published 3 policy statements on AIDS, the first in 1986 [1], the second in 1988 [2], and the third in 1994 [3]. In 2001, the IDSA created the HIV Medicine Association (HIVMA), and this updated policy paper is a collaboration between the ACP and the HIVMA of the IDSA. Since the last statement, many new developments call for the need to reexamine and update our policies relating to HIV infection. First, there have been major advances in treatment for HIV infection that have transformed HIV/AIDS from a terminal illness to a chronic disease for many of those who have access to potent therapies and expert medical care [4]. Second, there has been a profound expansion and intensification of the global HIV pandemic, particularly in sub-Saharan Africa, coupled with significant US leadership and resources aimed at providing prevention and care services to affected populations in developing countries. Third, the concerns that were prevalent in the mid-1990s regarding the possibility of HIV transmission in health care settings have ultimately proven to be unfounded as the result of the adoption of universal precautions in those settings. In this article, we emphasize the public health and clinical imperatives for earlier identification of persons with HIV infection; the urgent need to expand access to state-of-the-art HIV care and treatment for infected individuals; the need for access to comprehensive prevention and education for those living with and those at risk for HIV infection; and the need for stronger national leadership to respond to the HIV epidemic in the United States and in the developing world. In December 2008, the ACP and HIVMA released a guidance statement on screening for HIV infection in health care settings that recommended that clinicians adopt routine screening for HIV infection and encourage patients to be tested. Also included in the guidance statement is a recommendation that clinicians determine the need for additional screening on an individual basis

Recruitment of rare 3-grams at functional sites: Is this a mechanism for increasing enzyme specificity?

<p>Abstract</p> <p>Background</p> <p>A wealth of unannotated and functionally unknown protein sequences has accumulated in recent years with rapid progresses in sequence genomics, giving rise to ever increasing demands for developing methods to efficiently assess functional sites. Sequence and structure conservations have traditionally been the major criteria adopted in various algorithms to identify functional sites. Here, we focus on the distributions of the 20³different types of <it>3</it>-grams (or triplets of sequentially contiguous amino acid) in the entire space of sequences accumulated to date in the UniProt database, and focus in particular on the rare <it>3</it>-grams distinguished by their high entropy-based information content.</p> <p>Results</p> <p>Comparison of the UniProt distributions with those observed near/at the active sites on a non-redundant dataset of 59 enzyme/ligand complexes shows that the active sites preferentially recruit <it>3</it>-grams distinguished by their low frequency in the UniProt. Three cases, Src kinase, hemoglobin, and tyrosyl-tRNA synthetase, are discussed in details to illustrate the biological significance of the results.</p> <p>Conclusion</p> <p>The results suggest that recruitment of rare <it>3</it>-grams may be an efficient mechanism for increasing specificity at functional sites. Rareness/scarcity emerges as a feature that may assist in identifying key sites for proteins function, providing information complementary to that derived from sequence alignments. In addition it provides us (for the first time) with a means of identifying potentially functional sites from sequence information alone, when sequence conservation properties are not available.</p

Estimated Impact of Targeted Pre-Exposure Prophylaxis: Strategies for Men Who Have Sex with Men in the United States

Pre-exposure prophylaxis (PrEP) effectively reduces human immunodeficiency virus (HIV) transmission. We aimed to estimate the impact of different PrEP prioritization strategies among Black and Latino men who have sex with men (MSM) in the United States, populations most disproportionately affected by HIV. We developed an agent-based simulation to model the HIV epidemic among MSM. Individuals were assigned an HIV incidence risk index (HIRI-MSM) based on their sexual behavior. Prioritization strategies included PrEP use for individuals with HIRI-MSM &#8805;10 among all MSM, all Black MSM, young (&#8804;25 years) Black MSM, Latino MSM, and young Latino MSM. We estimated the number needed to treat (NNT) to prevent one HIV infection, reductions in prevalence and incidence, and subsequent infections in non-PrEP users avoided under these strategies over 5 years (2016&#8722;2020). Young Black MSM eligible for PrEP had the lowest NNT (NNT = 10) followed by all Black MSM (NNT = 33) and young Latino MSM (NNT = 35). All Latino MSM and all MSM had NNT values of 63 and 70, respectively. Secondary infection reduction with PrEP was the highest among young Latino MSM (53.2%) followed by young Black MSM (37.8%). Targeting all MSM had the greatest reduction in prevalence (14.7% versus 2.9%&#8722;3.9% in other strategies) and incidence (49.4% versus 9.4%&#8722;13.9% in other groups). Using data representative of the United States MSM population, we found that a strategy of universal PrEP use by MSM was most effective in reducing HIV prevalence and incidence of MSM. Targeted use of PrEP by Black and Latino MSM, however, especially those &#8804;25 years, had the greatest impact on HIV prevention

Protease inhibitors and cardiac autonomic function in hiv-infected patients: a cross-sectional analysis from the strategies for management of antiretroviral therapy (smart) trial

Objective: To compare cardiac autonomic function as measured by heart rate variability for HIV-infected participants taking protease inhibitors (PIs) with those taking a non-nucleoside reverse transcriptase inhibitor without a PI (NNRTI-no PI) regimen. Design: Cross-sectional analysis. Setting: Multicentre study. Participants: 2998 participants (average age 44 years, 28% females) enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial. Primary outcome measures: Heart rate and two heart rate variability measures (the SD of all filtered RR intervals over the length of the recording (SDNN) and the root mean square of successive differences in normal RR intervals (rMSSD)). Results: At study entry, 869 participants were taking a boosted PI (PI/r), 579 a non-boosted PI and 1550 an NNRTI-no PI. Median values (IQR) of heart rate, SDNN and rMSSD were: 68 (60-75) beats/min (bpm), 21 (13-33) ms, 22 (13-35) ms in the PI/r group, 68 (60-75) bpm, 21 (13-33) ms and 21 (14-33) ms in the non-boosted PI group and 69 (62-77) bpm, 20 (13-31) ms and 21(13-33) ms in the NNRTI-no PI group. After adjustment for baseline factors, for those given PI/r and nonboosted PI, heart rate was 2.2 and 2.8 bpm, respectively, lower than the NNRTI-no PI group (

Patterns and Correlates of Participant Retention in a Multi-City Pre-Exposure Prophylaxis Demonstration Project

Safe and effective use of pre-exposure prophylaxis (PrEP) depends on retention in care after initial engagement. The United States PrEP Demonstration Project offered daily oral tenofovir/emtricitabine to participants in San Francisco, Miami, and Washington, D.C. for 48 weeks from 2012 to 2014. The Demo Project participants' patterns of retention were assigned to 1 of 3 categories: early loss to follow-up (ELTF) within the first 12 weeks of the study, retention throughout the study, or intermittent retention in which missed or delayed visits resulted in gaps in medication availability. For each group, baseline characteristics were tabulated. A two-step multivariable analysis was performed. Overall, 366/554 (66.1%) of enrolled participants were retained for all study visits, 127/554 (22.9%) had intermittent retention, and 61/554 (11.0%) ELTF. In multivariable analysis, Miami compared with San Francisco site was associated with ELTF rather than full retention [aOR 2.84; confidence interval (CI): 1.24 to 6.47] and also with intermittent rather than full retention (aOR 2.70; CI: 1.43 to 5.11). Younger age was associated with ELTF (aOR 1.80 for each 10-year decrement in age; CI: 1.26 to 2.57) and intermittent retention (aOR 1.47; CI: 1.17 to 1.84) compared with full retention. Factors associated with ELTF (but not intermittent retention) compared with full retention were black compared with white (aOR 3.32; CI: 1.09 to 10.16), reporting sex work (aOR 4.67; CI: 1.49 to 14.58), lack of regular employment (aOR 2.53; CI: 1.27 to 5.05), and lack of previous PrEP awareness (aOR 2.01; CI: 1.01 to 3.96). Tailored interventions addressing causes and risk factors for loss from PrEP care may improve retention and consistency of PrEP use