Adherence to Daily Oral TDF/FTC for PrEP in Community Health Center Populations: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) Study.

The prevention effectiveness of oral preexposure prophylaxis (PrEP) is highly dependent on medication adherence but no validated longer term PrEP adherence measures are readily available for use by primary care clinicians caring for diverse populations. We compared two self-report measures (number of doses missed in past 7 days and day-by-day past week pill taking) to results of tenofovir concentrations in dried blood spot (DBS) samples at quarterly visits over the first 12 months of PrEP use. 1420 men and women in five US community health centers enrolled in a medication adherence substudy. For 3, 6, 9 and 12 months, the respective percentages of persons with self-report vs DBS levels consistent having taken all 7 doses in the week prior were 71% (51%), 70% (47%), 71% (46%) and 69% (44%). Conversely, the percentage of participants reporting taking 0-1 doses in the week prior by self-report vs DBS drug levels at 3, 6, 9 and 12 months consistent with this level of nonadherence of 6% (9%), 5% (10%), 8% (9%), and 9% (15%). The estimated risk of low adherence (estimated 0-1 doses in the week prior) was higher for participants of Black (RR 1.60, CI 1.09-2.34) or "Other" race (RR 1.62, CI 0.99-2.65) compared with participants of White race; being a transgender female (RR 2.31, CI 1.33-4.02) compared to men who have sex with men; or enrollment at a study site with less experience in the provision of PrEP. The estimated risk of low adherence by DBS was lower for participants with a higher number of sex partners in the past 3 months and those having a bachelor's degree or higher. More work is needed to provide clinicians with measures to assess medication adherence in diverse US populations being prescribed PrEP to support its effective use in reducing HIV acquisition in individuals and at the community level.

Measurement of plasma HIV-1 RNA below the limit of quantification (<20 copies/mL) of commercial assays with the integrase HIV RNA single-copy assay.

BACKGROUND: Plasma HIV-1 RNA (viral load, VL) is measured routinely in HIV-infected persons with FDA-approved commercially available assays such as the Cobas-TaqMan HIV-1 Assay v2.0. This assay provides quantification of viremia ≥20 copies/mL. More sensitive methods, able to quantify low-level persistent viremia below the detection limit of commercially available assays, are needed to assess the impact of current HIV cure strategies on viremia. OBJECTIVES: The novel integrase HIV-1 RNA single-copy assay (iSCA) was evaluated for measurement of low-level persistent viremia in clinical trial samples (n = 151) from subjects participating in Gilead HIV clinical research. STUDY DESIGN: Paired plasma samples from HIV-1-infected patients treated with combination ART were assessed using both HIV-1 Cobas-TaqMan and iSCA; results from the two assays were compared. RESULTS: Paired Cobas-TaqMan/iSCA data were obtained for 151 HIV-infected adults. Most samples (117/151, 77%) had non-quantifiable Cobas-TaqMan result, either <20 copies/mL ("<20") or "Target Not Detected" (TND). All 117 non-quantified samples were quantified with iSCA and showed higher HIV-1 RNA levels in samples with <20 than TND Cobas-TaqMan results (p < 0.0001). CONCLUSIONS: In this large sample collection from virologically suppressed HIV-infected adults, use of iSCA led to quantification of low-level viremia below the limit of detection of the Cobas-TaqMan assay in all 117 previously non-quantifiable plasma samples. These data confirm the value of the iSCA as a helpful addition to the classical HIV VL assays and its potential for use in HIV cure studies to assess whether experimental interventions alter viremia.

Response to Comment on "Dissolved organic sulfur in the ocean: Biogeochemistry of a petagram inventory".

Dittmar et al proposed that mixing alone can explain our observed decrease in marine dissolved organic sulfur with age. However, their simple model lacks an explanation for the origin of sulfur-depleted organic matter in the deep ocean and cannot adequately reproduce our observed stoichiometric changes. Using radiocarbon age also implicitly models the preferential cycling of sulfur that they are disputing.

Dissolved organic sulfur in the ocean: Biogeochemistry of a petagram inventory.

Although sulfur is an essential element for marine primary production and critical for climate processes, little is known about the oceanic pool of nonvolatile dissolved organic sulfur (DOS). We present a basin-scale distribution of solid-phase extractable DOS in the East Atlantic Ocean and the Atlantic sector of the Southern Ocean. Although molar DOS versus dissolved organic nitrogen (DON) ratios of 0.11 ± 0.024 in Atlantic surface water resembled phytoplankton stoichiometry (sulfur/nitrogen ~ 0.08), increasing dissolved organic carbon (DOC) versus DOS ratios and decreasing methionine-S yield demonstrated selective DOS removal and active involvement in marine biogeochemical cycles. Based on stoichiometric estimates, the minimum global inventory of marine DOS is 6.7 petagrams of sulfur, exceeding all other marine organic sulfur reservoirs by an order of magnitude.

Selective consumption and metabolic allocation of terrestrial and algal carbon determine allochthony in lake bacteria.

Here we explore strategies of resource utilization and allocation of algal versus terrestrially derived carbon (C) by lake bacterioplankton. We quantified the consumption of terrestrial and algal dissolved organic carbon, and the subsequent allocation of these pools to bacterial growth and respiration, based on the δ(13)C isotopic signatures of bacterial biomass and respiratory carbon dioxide (CO2). Our results confirm that bacterial communities preferentially remove algal C from the terrestrially dominated organic C pool of lakes, but contrary to current assumptions, selectively allocate this autochthonous substrate to respiration, whereas terrestrial C was preferentially allocated to biosynthesis. The results provide further evidence of a mechanism whereby inputs of labile, algal-derived organic C may stimulate the incorporation of a more recalcitrant, terrestrial C pool. This mechanism resulted in a counterintuitive pattern of high and relatively constant levels of allochthony (~76%) in bacterial biomass across lakes that otherwise differ greatly in productivity and external inputs.

Evidence for the respiration of ancient terrestrial organic C in northern temperate lakes and streams.

Northern rivers and lakes process large quantities of organic and inorganic carbon from the surrounding terrestrial ecosystems. These external carbon inputs fuel widespread CO(2) supersaturation in continental waters, and the resulting CO(2) emissions from lakes and rivers are now recognized as a globally significant loss of terrestrial production to the atmosphere. Whereas the magnitude of emissions has received much attention, the pathways of C delivery and processing that generate these emissions are still not well-understood. CO(2) outgassing in aquatic systems has been unequivocally linked to microbial degradation and respiration of terrestrial organic carbon (OC), but the nature (i.e., age and source) of this OC respired in surface waters is largely unknown. We present direct radiocarbon measurements of OC respired by bacteria in freshwater aquatic systems, specifically temperate lakes and streams in Québec. Terrestrial OC fuels much of the respiration in these systems, and our results show that a significant fraction of the respired terrestrial OC is old (in the range of 1,000-3,000 y B.P.). Because the bulk OC pools in these lakes is relatively young, our results also suggest selective removal of an old but highly bioreactive terrestrial OC pool and its conversion to CO(2) by bacteria. The respiration of ancient (14)C-depleted terrestrial C in northern lakes and rivers provides a biological link between contemporary aquatic carbon biogeochemistry and paleo-conditions in the watershed, and it implies the aquatic-mediated return to the atmosphere of C putatively considered permanently stored, thus challenging current models of long-term C storage in terrestrial reservoirs.

Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART.

OBJECTIVE: To determine if low level, persistent, HIV-1 replication within specific immune cells contributes to HIV-1-specific immune responsiveness. DESIGN: We analyzed 59 HIV-1-infected subjects on stable highly active antiretroviral therapy (HAART) therapy (not including zidovudine) with suppressed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function. METHODS: Peripheral blood mononuclear cells were collected for immunophenotyping, lymphoproliferative assays, and simultaneous immunophenotyping/ultrasensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive statistics (mean and SD, median, first and third quartiles) were determined for all variables in two groups defined as having persistent viral replication present or absent. The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups. RESULTS: HIV-1 replication in CD4, CD45RO memory T lymphocytes persists in spite of undetectable plasma viral load. Patients (n = 24) with persistent intracellular expression of HIV-1 mRNA (> 0.3%) showed significant in vitro proliferative responses to HIV-1 p24 (stimulation index > or = 10) compared to patients (n = 35) without persistent intracellular replication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend toward higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infections; however, the high viral persistence group was more HAART experienced (P < 0.05). CONCLUSIONS: These results suggest that HIV-1-specific immune responses correlate with evidence of ongoing HIV-1 replication.

Women, disability, and sport and physical fitness activity: the intersection of gender and disability dynamics.

This study explores the often overlooked experiences of women with physical disabilities in the sport and physical fitness activity domain. Interviews with 16 women with a physical disability (age range of 19-54 years) revealed the following major themes: (a) participation in fitness-related as opposed to sport-related activities, (b) participation to maintain the functional level of the body and preserve existing capabilities, (c) intrinsic nature of gains derived from participation (perceived competence, enhanced view of body, motivational outlet, control in life), and (d) perceived differences in the sport and physical fitness activity experiences of men and women with disabilities. Findings support the notion that gender and disability interact in the sport and physical fitness context for women with physical disabilities.

Focus group discussions -- a tool for learning and organizing.

PIP: This article describes how to design focus groups, recruit participants, prepare questions for discussion, train facilitators, conduct sessions, and share results with the community. The description is based on the Community Life Project's (CLP) (Lagos, Nigeria) experiences since 1992, with using focus group discussions (FGDs) to teach women how to negotiate safe sex and prevent HIV/AIDS. CLP focused on several target populations and set up a team to recruit participants. Participants were recruited on the basis of age, gender, income, residence for at least 10 years in the community, willingness to discuss sex and sexuality, and interest in quality of life issues. Each of the 25 FGDs were formed with a mixture of characteristics among 8-10 persons. 12 facilitators were trained. 4 persons took notes. Participants were recruited through a wide network of schools, trade and professional associations, hotels, health facilities, social clubs, and church groups. The team contacted each identified participant and asked about their willingness and convenient meeting times. Formal invitations with a time and place were delivered and participation was confirmed. The team developed a discussion guide with questions that were field tested. FGDs began with a welcoming. People were encouraged to express ideas in confidence within the FGD and to ignore the rightness or wrongness of answers. FGDs met for as long as 2 hours. CLP discussed the FGD findings at community meetings. One finding was that FGDs offered open talk about a difficult topic.^ieng

Social support in the athletic training room: athletes' expectations of staff and student athletic trainers.

OBJECTIVE: Social support has been identified repeatedly in the literature as being beneficial to individuals suffering from injury or illness. Because of the frequent interaction between athletic trainers and student athletes, the athletic trainer is in a unique position to provide a variety of social support to the athlete. The purpose of the study was (1) to identify the degree to which athletes actually receive each of eight types of social support; (2) to identify the types of social support athletes need or expect to receive from staff and student athletic trainers; and (3) to compare the athletes' satisfaction with the quality of the support received from athletic training staff and students. DESIGN AND SETTING: A questionnaire was used to collect data for this study. It was administered at a Division I university. SUBJECTS: Eighty-five student-athletes at a Division I university. MEASUREMENTS: The survey consisted of 24 questions that used a five-point Likert rating scale. RESULTS: There was no significant difference in the amount of social support received by athletes from staff and student athletic trainers, in athletes' expectations of staff and student athletic trainers with regard to provision of social support, or in the athletes' level of satisfaction with staff and student athletic trainers' provision of social support. CONCLUSIONS: Examined collectively, the findings indicate that athletes do not differentiate between staff and student athletic trainers with regard to the provision of social support. However, finding that athletes do not differentiate between staff and student athletic trainers in this area is significant in itself and has implications for athletic training education programs.

HIV-related sinusitis: nothing to sniff at.

HIV-positive people are particularly susceptible to sinusitis, acute or chronic, and the severity of attacks increases as a person's CD4 count declines. Chronic sinusitis may, in fact, be an early manifestation of HIV infection and can even be asymptomatic. HIV-infected people should minimize the risks of contracting sinusitis by treating any minor respiratory infection as potentially significant and keeping tabs on allergies.

Radiation exposure: comparison of rapid exchange and conventional over-the-wire coronary angioplasty systems.

The growth of coronary angioplasty has resulted in increased fluoroscopy time to patients, staff, and physicians. Rapid exchange-type catheters have purported to reduce fluoroscopy time and procedure time compared to conventional over-the-wire systems. Of 150 consecutive patients, 54 were treated solely with rapid-exchange catheters and 84 were treated solely with over-the-wire catheters. Excluding 12 cases treated with fixed wire or combination catheters, the following data were found: [table: see text] Overall procedural success was obtained in 98.5% (136/138) of patients, 1.5% (2) requiring emergency coronary artery bypass graft surgery. A significant 35% reduction in fluoroscopy time and 13% reduction in procedure time were found when rapid-exchange catheters were used, with identical success rates, number of balloons used per case, and complication rates compared to over-the-wire catheters. Rapid-exchange catheters should be considered as part of an overall effort to reduce radiation exposure in the interventional cardiology laboratory.

Effects of alterations in systolic pressure on radionuclide measurements of left ventricular filling dynamics.

To determine the effects of steady-state left ventricular systolic pressure alterations on radionuclide measures of left ventricular filling dynamics, we studied 15 normal patients and 17 patients with nonischemic heart disease. Micromanometer left ventricular pressures and computer assisted forward gated radionuclide angiograms were acquired simultaneously. Right atrial pacing maintained heart rates constant during the baseline condition and methoxamine and nitroprusside infusions. Diastolic filling dynamics, peak filling rate and time to peak filling rate were calculated using a three harmonic Fourier analysis of the left ventricular time-activity curves. Left ventricular systolic pressure increased to 165 +/- 25 mmHg with methoxamine (p < 0.001) and decreased to 106 +/- 18 mmHg with nitroprusside (p < 0.001) from a baseline value of 133 +/- 16 mmHg. Radionuclide left ventricular filling dynamics did not change significantly. Thus, we conclude that radionuclide measurements of left ventricular filling dynamics are not affected by modest, steady-state alterations in left ventricular systolic pressure and can therefore be useful for the assessment of left ventricular diastolic function during interventions which may also affect left ventricular systolic pressure.