Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

Concomitant socioeconomic, behavioral, and biological factors associated with the disproportionate HIV infection burden among black men who have sex with men in 6 U.S. cities

Background American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood. Methods Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV. Results HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6th(16.2%) were previously diagnosed with HIV (PD); of 1263 participants without a prior HIV diagnosis 7.6% were newly diagnosed (ND). Compared to PD, ND Black MSM were younger (p Conclusions ND HIV-infected Black MSM were more likely to be unemployed, have bacterial STIs and engage in URAI than other Black MSM. Culturally-tailored programs that address economic disenfranchisement, increase engagement in care, screen for STIs, in conjunction with safer sex prevention interventions, may help to decrease further transmission in this heavily affected community

Knowledge brokering between researchers and policymakers in Fiji to develop policies to reduce obesity: a process evaluation

The importance of using research evidence in decision making at the policy level has been increasingly recognized. However, knowledge brokering to engage researchers and policymakers in government and non-government organizations is challenging. This paper describes and evaluates the knowledge exchange processes employed by the Translational Research on Obesity Prevention in Communities (TROPIC) project that was conducted from July 2009 to April 2012 in Fiji. TROPIC aimed to enhance: the evidence-informed decision making skills of policy developers; and awareness and utilization of local and other obesity-related evidence to develop policies that could potentially improve the nation&rsquo;s food and physical activity environments. The specific research question was: Can a knowledge brokering approach advance evidence-informed policy development to improve eating and physical activity environments in Fiji. <br /

Multidrug-Resistant Tuberculosis in Patients without HIV Infection

BACKGROUND Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. METHODS We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis--defined as tuberculosis resistant at least to isoniazid and rifampin--who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. RESULTS Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). CONCLUSIONS In this report from New York City, HIV-negative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically

Discontinuation of Prophylaxis against Mycobacterium avium Complex Disease in HIV-Infected Patients Who Have a Response to Antiretroviral Therapy

BACKGROUND Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. METHODS We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. RESULTS A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). CONCLUSIONS Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy

Infrequent HIV Testing and Late HIV Diagnosis Are Common Among a Cohort of Black Men Who Have Sex With Men in 6 US Cities

Objective: US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM). Methods: HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count <200 cells per cubic millimeter or <350 cells per cubic millimeter at diagnosis. Results: HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no previous HIV diagnosis; 272 (21.2%) reported no HIV test in previous 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the previous 6 months (relative risk [RR]: 1.08, 95% confidence interval [CI]: 1.03 to 1.13), being unemployed (RR: 1.04, CI: 1.01 to 1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0 to 1.05). New HIV diagnoses were more likely among infrequent testers compared with men tested in the previous year (18.4% vs. 4.4%; odds ratio: 4.8, 95% CI: 3.2 to 7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells per cubic millimeter including 17 (20.2%) with CD4 <200 cells per cubic millimeter. Conclusions: Infrequent HIV testing, undiagnosed infection, and late diagnosis were common among BMSM in this study. New HIV diagnoses were more common among infrequent testers, underscoring the need for additional HIV testing and prevention efforts among US BMSM. Infrequent HIV Testing and Late HIV Diagnosis Are Common Among a Cohort of Black Men Who Have Sex With Men in 6 US Cities. Available from: https://www.researchgate.net/publication/265419180_Infrequent_HIV_Testing_and_Late_HIV_Diagnosis_Are_Common_Among_a_Cohort_of_Black_Men_Who_Have_Sex_With_Men_in_6_US_Cities [accessed Feb 4, 2016]

Discovery of genetic variants of the kinases that activate tenofovir among individuals in the United States, Thailand, and South Africa: HPTN067

Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two phosphorylation steps to form a competitive inhibitor of HIV reverse transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA isolated from dried blood spots collected from 505 participants from Bangkok, Thailand; Cape Town, South Africa; and New York City, USA were examined for variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals (3.7% frequency) carried variants in at least one kinase that would result in a decrease or loss of enzymatic activity. To functionally test these predictions, AK2 and AK2 variants were expressed in and purified from E. coli, followed by investigation of their activities towards tenofovir. Interestingly, we found that purified AK2 had the ability to phosphorylate tenofovir-monophosphate to tenofovir-diphosphate in addition to phosphorylating tenofovir to tenofovir-monophosphate. Further, four of the six AK2 variants predicted to result in a loss or decrease of enzyme function exhibited a ≥30% decrease in activity towards tenofovir in our in vitro assays. Of note, an AK2 K28R variant resulted in a 72% and 81% decrease in the formation of tenofovir-monophosphate and tenofovir-diphosphate, respectively. These data suggest that there are naturally occurring genetic variants that could potentially impact TFV activation

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion

<p>Abstract</p> <p>Background</p> <p>Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion.</p> <p>Methods</p> <p>Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode.</p> <p>Results</p> <p>In group 1 the Pw/Pa ratio decreased by 10 ± 22% from 0.20 ± 0.09 to 0.19 ± 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 ± 15% from 0.22 ± 0.09 to 0.24 ± 0.10 (p = 0.001) when electrical neurostimulation was activated.</p> <p>Conclusion</p> <p>Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.</p

Limited awareness of pre-exposure prophylaxis among black men who have sex with men and transgender women in New York City

Awareness of Pre-exposure prophylaxis (PrEP) was assessed among a cohort of substance-using black men who have sex with men and transgender women (MSM/TGW) participating in the STAR Study, which recruited black MSM/TGW in New York City for HIV testing and linked HIV-infected individuals into care from July 2012 to April 2015. Sociodemographic, psychosocial, known HIV risk factors, and PrEP awareness were assessed among participants. Multivariable logistic regression was conducted to assess factors associated with PrEP awareness. Of 1673 participants, median age was 43 years and 25% were under age 30. Most participants (85.8%) reported having insufficient income for basic necessities at least occasionally, 54.8% were homeless, and 71.3% were unemployed. Awareness of PrEP was reported among 18.2% of participants. PrEP awareness was associated with younger age (adjusted odds ratio [aOR] 0.87, per 5 years), gay identity (aOR 2.46), higher education (aOR 1.70), more frequent past HIV testing (aOR 3.18), less HIV stigma (aOR 0.61), less hazardous/harmful alcohol use (aOR 0.61), and more sexual partners (aOR 1.04, per additional partner in past 30 days). In this substance-using black MSM/TGW cohort with high rates of poverty and homelessness, PrEP awareness was low. This study demonstrates the need for targeted dissemination of PrEP information to key populations to increase awareness and ultimately improve uptake and utilization of PrEP

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

Background: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits. Results: Men with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment. Conclusions: HIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load