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1.
Sex Transm Dis ; 47(1): 5-11, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31658242

RESUMO

The goal of the STAR Sexually Transmitted Infection Clinical Trial Group (STI CTG) Programmatic meeting on Sexually Transmitted Infections (STIs) in Pregnancy and Reproductive Health in April 2018 was to review the latest research and develop recommendations to improve prevention and management of STIs during pregnancy. Experts from academia, government, nonprofit, and industry discussed the burden of STIs during pregnancy; the impact of STIs on adverse pregnancy and birth outcomes; interventions that work to reduce STIs in pregnancy, and the evidence, policy, and technology needed to improve STI care during pregnancy. Key points of the meeting are as follows: (i) alternative treatments and therapies for use during pregnancy are needed; (ii) further research into the relationship between the vaginal microbiome and STIs during pregnancy should be supported; (iii) more research to determine whether STI tests function equally well in pregnant as nonpregnant women is needed; (iv) development of new lower cost, rapid point-of-care testing assays could allow for expanded STI screening globally; (v) policies should be implemented that create standard screening and treatment practices globally; (vi) federal funding should be increased for STI testing and treatment initiatives supported by the Centers for Disease Control and Prevention (CDC), the Centers of Excellence in STI Treatment, public STD clinics, and the President's Emergency Plan for AIDS Relief (PEPFAR).

2.
Clin Infect Dis ; 70(1): 140-143, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074488

RESUMO

Cannabis use is frequent among people living with human immunodeficiency virus (HIV) and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to those with no drug use. No cannabis effect was observed on cellular HIV RNA transcription.

3.
Medicine (Baltimore) ; 98(50): e18232, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852085

RESUMO

Transgender people continue to be at high-risk for HIV acquisition, but little is known about the characteristics of their sexual partners. To address this gap, we examined sociodemographic and sexual characteristics of cisgender men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) reporting transgender sexual partners.A cohort of 392 MSM in southern California in a randomized clinical trial for PrEP adherence were followed from 2013 to 2016. Multivariable generalized estimating equation and logistic models identified characteristics of MSM reporting transgender sexual partners and PrEP adherence.Only 14 (4%) MSM reported having transgender sexual partners. MSM were more likely to report transgender partners if they were African American, had incident chlamydia, reported injection drug-using sexual partners, or received items for sex. Most associations remained significant in the multivariable model: African American (adjusted odds ratio [AOR] 11.20, P = .01), incident chlamydia (AOR 3.71, P = .04), and receiving items for sex (AOR 5.29, P = .04). There were no significant differences in PrEP adherence between MSM reporting transgender partners and their counterpart.MSM who report transgender sexual partners share characteristics associated with individuals with high HIV prevalence. Identifying this group distinct from larger cohorts of MSM could offer new HIV prevention opportunities for this group of MSM and the transgender community.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Prevenção Primária/métodos , Comportamento Sexual , Parceiros Sexuais , Pessoas Transgênero , Adulto , Seguimentos , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , Adesão à Medicação , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
4.
Pathogens ; 8(4)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569735

RESUMO

This study aimed to determine the presence of giardiasis among HIV patients in San Diego, the rate of failure of metronidazole treatment, and factors associated with treatment failure. We used a 7 year retrospective single-center case series of HIV-infected individuals with giardiasis at University of California San Diego Medical Center. Data were analyzed for the changes in the hematological, biochemical, and immunologic results at pre- and at-diagnosis levels. We also compared the changes at the diagnosis level among patients who were treated successfully and those who experienced treatment failure as defined by retreatment with a second course of antibiotics. In 29 Giardia lamblia-infected HIV patients, following diagnosis of G. lamblia, there was a non-significant decrement in cluster of differentiation 4 (CD4), but a statistically significant increase in the number of white blood cell (WBC). Other indices did not differ between pre- and at-diagnosis levels. Twenty patients (69%) were treated with a single course of metronidazole or tinidazole and seven patients (24.1%) were treated with more than one course of metronidazole. These seven patients had statistically significant higher hemoglobin at the time of diagnosis, but further studies are required to confirm if this is a consistent finding and if this can predict failure from primary therapy.

5.
Sex Health ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296280

RESUMO

Background:Most studies evaluating extragenital testing performance for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection by the Xpert® CT/NG show high per cent agreement with comparison assays; however, the precision around positive per cent agreement is low and thus the values that have been reported are not highly informative. Therefore, a systematic review was conducted and data from five studies were combined to better assess positive per cent agreement. Methods: The literature indexed on PubMed.gov was searched. Included studies were those that were an evaluation of the Xpert CT/NG assay with rectal and/or pharyngeal specimen types compared with another nucleic acid amplification test (NAAT), the Aptima transcription mediated amplification assay. A full Bayesian method was used for bivariate fixed-effect meta-analysis of positive and negative per cent agreement and pooled estimates (and 95% confidence intervals (CI)) were presented for each. Results: The pooled positive and negative per cent agreement for detection of CT in rectal specimens was 89.72% (95% CI: 84.97%, 93.64%) and 99.23% (95% CI: 98.74%, 99.60%), and in pharyngeal specimens, they were 89.96% (95% CI: 66.38%, 99.72%) and 99.62% (95% CI: 98.95%, 99.95%) respectively. For NG detection in rectal specimens, the pooled positive and negative per cent agreement was 92.75% (95% CI: 87.91%, 96.46%) and 99.75% (95% CI: 99.46%, 99.93%), and in pharyngeal specimens, they were 92.51% (95% CI: 85.84%, 97.18%) and 98.56% (95% CI: 97.69%, 99.23%) respectively. Conclusions: It was found that the Xpert CT/NG assay performed similarly to the Aptima transcription mediated amplification assay for the detection of CT and NG in extragenital specimens. The Xpert assay has the benefit of providing faster results at the point-of-care, thus reducing the turnaround time for results, potentially enabling same-day treatment.

6.
AIDS Patient Care STDS ; 33(5): 220-226, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31067122

RESUMO

Men who have sex with men (MSM) reporting higher HIV risk behavior over time are often more adherent to pre-exposure prophylaxis (PrEP), but it is unclear if recent risk behavior and partnership type affect long-term PrEP adherence. HIV-negative MSM and transgender women completing the 48-week randomized study TAPIR (Daily Text Messages to Support Adherence to PrEP in At-Risk for HIV Individuals) were included. At baseline and weeks 24 and 48, a modified Calculated Risk (mCalcR) Score estimated the likelihood of HIV seroconversion over 1 year based on reported condomless anal sex acts in the last month and current sexually transmitted infection. mCalcR scores were categorized as low, moderate, and high/very high risk. Partnership type was classified as no partner/single HIV-negative partner (no/single-), single HIV-positive partner (single+), or multiple partners of any serostatus (multi) in the past 3 months. PrEP adherence was measured by intracellular tenofovir-diphosphate (TFV-DP) levels. Among 313 individuals, there was no difference in mCalcR category from baseline to week 48. There was a significant change in partnership type, with no/single partnerships increasing from 0.5% to 9%. Participants with moderate and high/very risk had higher TFV-DP levels than the low-risk group. No/single participants had lower TFV-DP levels than those reporting single+ or multi. Although there was a shift toward lower-risk partnerships, HIV risk category remained stable over time. Individuals with riskier behaviors and partnerships had higher PrEP drug levels, suggesting continued motivation for and adherence to PrEP.

7.
J Acquir Immune Defic Syndr ; 81(2): 166-174, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30865175

RESUMO

BACKGROUND: Efficacy of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men is well documented in randomized trials. After trial completion, participants are challenged with acquiring PrEP on their own and remaining adherent. METHODS: This was a follow-up study of the TAPIR randomized controlled multicenter PrEP trial. Participants were contacted after their last TAPIR visit (ie, after study-provided PrEP was discontinued) to attend observational posttrial visits 24 and 48 weeks later. Adherence during TAPIR and posttrial visits was estimated by dried blood spot intracellular tenofovir diphosphate levels (adequate adherence defined as tenofovir diphosphate levels >719 fmol/punch). Binary logistic regression analysis assessed predictors of completing posttrial visits and PrEP adherence among participants completing ≥1 visit. RESULTS: Of 395 TAPIR participants who were on PrEP as part of the TAPIR trial for a median of 597 days (range 3-757 days), 122 (31%) completed ≥1 posttrial visit (57% of University of California San Diego participants completed posttrial visits, whereas this was 13% or lower for other study sites). Among participants who completed ≥1 posttrial visit, 57% had adequate adherence posttrial. Significant predictors of adequate adherence posttrial were less problematic substance use, higher risk behavior, and adequate adherence in year 1 of TAPIR. CONCLUSION: More than half of PrEP users followed after trial completion had successfully acquired PrEP and showed adequate adherence. Additional adherence monitoring and intervention measures may be needed for those with low PrEP adherence and problematic substance use during the first year of trial.

8.
Lancet HIV ; 6(3): e164-e172, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30765313

RESUMO

BACKGROUND: Transgender women are among the groups at highest risk for HIV infection, with a prevalence of 27·7% in the USA; and despite this known high risk, undiagnosed infection is common in this population. We set out to identify transgender women and their partners in a molecular transmission network to prioritise public health activities. METHODS: Since 2006, HIV protease and reverse transcriptase gene (pol) sequences from drug resistance testing have been reported to the Los Angeles County Department of Public Health and linked to demographic data, gender, and HIV transmission risk factor data for each case in the enhanced HIV/AIDS Reporting System. We reconstructed a molecular transmission network by use of HIV-TRAnsmission Cluster Engine (with a pairwise genetic distance threshold of 0·015 substitutions per site) from the earliest pol sequences from 22 398 unique individuals, including 412 (2%) self-identified transgender women. We examined the possible predictors of clustering with multivariate logistic regression. We characterised the genetically linked partners of transgender women and calculated assortativity (the tendency for people to link to other people with the same attributes) for each transmission risk group. FINDINGS: 8133 (36·3%) of 22 398 individuals clustered in the network across 1722 molecular transmission clusters. Transgender women who indicated a sexual risk factor clustered at the highest frequency in the network, with 147 (43%) of 345 being linked to at least one other person (adjusted odds ratio [aOR] 2·0, p=0·0002). Transgender women were assortative in the network (assortativity 0·06, p<0·001), indicating that they tended to link to other transgender women. Transgender women were more likely than expected to link to other transgender women (OR 4·65, p<0·001) and cisgender men who did not identify as men who have sex with men (MSM; OR 1·53, p<0·001). Transgender women were less likely than expected to link to MSM (OR 0·75, p<0·001), despite the high prevalence of HIV among MSM. Transgender women were distributed across 126 clusters, and cisgender individuals linked to one transgender woman were 9·2 times more likely to link to a second transgender woman than other individuals in the surveillance database. Reconstruction of the transmission network is limited by sample availability, but sequences were available for more than 40% of diagnoses. INTERPRETATION: Clustering of transgender women and the observed tendency for linkage with cisgender men who did not identify as MSM, shows the potential to use molecular epidemiology both to identify clusters that are likely to include undiagnosed transgender women with HIV and to improve the targeting of public health prevention and treatment services to transgender women. FUNDING: California HIV and AIDS Research Program and National Institutes of Health-National Institute of Allergy and Infectious Diseases.

9.
J Neurovirol ; 25(3): 324-330, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30617849

RESUMO

The objective of this study was to examine differences in the levels of risky decision making and other frontal system behavior constructs in relation to self-initiated continuance of HIV pre-exposure prophylaxis (PrEP) and PrEP adherence outcomes among men who have sex with men (MSM) following completion of a clinical PrEP trial. At the last PrEP trial visit, study provided PrEP was discontinued and participants were navigated to the community for PrEP continuation. In this cross-sectional analysis, 84/187 (45%) MSM who completed a prospective observational post-PrEP trial follow-up visit at the University of California San Diego were included. PrEP adherence was measured using dried blood spot tenofovir diphosphate (TFV-DP) levels. Risky decision making was assessed using the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), while impulsivity/disinhibition, sensation seeking, and substance use were assessed via standardized self-report questionnaires. A total of 58/84 (69%) of MSM who completed the 12-month post-study visit continued PrEP. Of those, n = 46 (79%) reached TFV-DP levels associated with adequate adherence. Individuals who elected to continue PrEP 12 months post-trial had riskier decision making on BART, but less impulsivity/disinhibition compared to individuals who did not continue PrEP. Neither risky decision making nor impulsivity/disinhibition/sensation seeking nor substance use correlated with PrEP adherence. Our findings suggest that those with risky decision making may have greater insight into their HIV risks, and therefore be more likely to continue to use PrEP. However, elevated impulsivity/disinhibition, indicative of greater neurobehavioral alterations, was negatively associated with PrEP continuance and is a potential target for future interventions to help people link to PrEP.

10.
J Acquir Immune Defic Syndr ; 80(1): e9-e13, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30334877

RESUMO

BACKGROUND: A public health concern regarding HIV pre-exposure prophylaxis (PrEP) is sexual risk compensation (ie, increased unsafe sex among PrEP users that may undermine prevention efforts). METHODS: This demonstration study (NCT#01761643; initiated in 2013) included 398 men who have sex with men who initiated PrEP and were followed over 48 weeks at 4 sites in Southern California. Wilcoxon signed-rank tests compared previous 30-day number of sex partners and condomless insertive anal sex and receptive anal sex (CIAS and CRAS, respectively) acts at weeks 4, 12, 24, 36, and 48 to baseline. At 2 sites, PrEP users were also compared with a lagged, comparison group of 99 men who have sex with men who did not receive PrEP over 24 weeks using linear regression models, adjusting for age, race/ethnicity, education, and respective baseline scores. Logistic regression compared week 24 sexually transmitted infection (STI) rates. RESULTS: Over 48 weeks in the PrEP group, there were significant decreases in the number of unknown HIV status sex partners and increases in CRAS at all study visits; there was no consistent change in number of HIV+ sex partners or CIAS. Among participants at 2 sites, there were no significant differences between PrEP and non-PrEP users in change in number of partners, CIAS, CRAS, or STI rates at week 24. CONCLUSIONS: Among early adopters of PrEP, there is some evidence for sexual risk compensation. Results support current guidelines of regular STI screening and behavioral risk reduction and adherence counseling with the provision of PrEP.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição , Tenofovir/uso terapêutico , Sexo sem Proteção/estatística & dados numéricos , Adulto , Aconselhamento Diretivo , Feminino , Infecções por HIV/psicologia , Inquéritos Epidemiológicos , Homossexualidade Masculina , Humanos , Masculino , Modelos Teóricos , Pessoas Transgênero , Sexo sem Proteção/psicologia
11.
Sex Transm Dis ; 46(3): e18-e25, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30363025

RESUMO

The goal of the Sexually Transmitted Infection Clinical Trial Group's Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, nonprofit and industry to discuss the current state of research, gaps and challenges in research and technology and priorities and new directions to address the continued emergence of multidrug-resistant NG infections. Topics discussed at the meeting, which will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG; (ii) the US National Strategy for combating antimicrobial-resistant bacteria; (iii) surveillance needs, challenges, and novel technologies; (iv) plasmid-mediated and chromosomally mediated mechanisms of AMR in NG; (v) novel therapeutic (eg, sialic acid analogs, factor H [FH]/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (eg, peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives, and collaborations across academic and commercial research and public health programs.

12.
J Infect Dis ; 218(10): 1551-1559, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30295803

RESUMO

Background: Adherence is necessary for efficacy of preexposure prophylaxis (PrEP), and text-messaging methods are promising tools for both adherence assessment and support. Although PrEP adherence is variable, little research has examined patterns of variability or factors associated with longitudinal use. Methods: In the context of a randomized controlled trial of text-messaging versus standard of care for PrEP adherence, 181 men who have sex with men received once-daily tenofovir disoproxil fumarate/emtricitabine and daily adherence texts for 48 weeks. Growth mixture modeling (GMM) was used to identify subgroups of individuals with similar trajectories of text-reported adherence. Between-group differences in pharmacologic measures of adherence (ie, tenofovir diphosphate and emtricitabine triphosphate levels), as well as predictors and study-end attitudes associated with group membership, were examined. Results: GMM identified 4 trajectories of text-reported adherence. Classes with higher text-reported adherence had higher drug concentrations. Younger age and minority race were associated with lower adherence, and individuals in classes with lower adherence had greater baseline levels of depression, substance use concerns, and sexual risk. Differences in study satisfaction were also associated with adherence. Conclusions: This study supports the use of text-reported PrEP adherence. Identifying factors associated with less-than-optimal adherence may aid clinicians in anticipating at-risk patients requiring augmented intervention. Clinical trials registration: NCT01761643.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Adesão à Medicação/estatística & dados numéricos , Profilaxia Pré-Exposição/métodos , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Masculino , Mensagem de Texto , Adulto Jovem
13.
Sci Rep ; 8(1): 15212, 2018 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-30315206

RESUMO

Daily PrEP is highly effective at preventing HIV-1 acquisition, but risks of long-term tenofovir disoproxil fumarate plus emtricitabine (TDF-FTC) include renal decline and bone mineral density decrease in addition to initial gastrointestinal side effects. We investigated the impact of TDF-FTC on the enteric microbiome using rectal swabs collected from healthy MSM before PrEP initiation and after 48 to 72 weeks of adherent PrEP use. The V4 region of the 16S ribosomal RNA gene sequencing showed that Streptococcus was significantly reduced from 12.0% to 1.2% (p = 0.036) and Erysipelotrichaceae family was significantly increased from 0.79% to 3.3% (p = 0.028) after 48-72 weeks of daily PrEP. Catenibacterium mitsuokai, Holdemanella biformis and Turicibacter sanguinis were increased within the Erysipelotrichaceae family and Streptococcus agalactiae, Streptococcus oralis, Streptococcus mitis were reduced. These changes were not associated with host factors including PrEP duration, age, race, tenofovir diphosphate blood level, any drug use and drug abuse, suggesting that the observed microbiome shifts were likely induced by daily PrEP use. Long-term PrEP resulted in increases of Catenibacterium mitsuokai and Holdemanella biformis, which have been associated with gut microbiome dysbiosis. Our observations can aid in characterizing PrEP's side effects, which is likely to improve PrEP adherence, and thus HIV-1 prevention.


Assuntos
Emtricitabina/farmacologia , HIV-1/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Profilaxia Pré-Exposição , Reto/microbiologia , Streptococcus/efeitos dos fármacos , Tenofovir/farmacologia , Adulto , Biodiversidade , Esquema de Medicação , Emtricitabina/administração & dosagem , Erysipelothrix , Feminino , Humanos , Pessoa de Meia-Idade , Especificidade da Espécie , Tenofovir/administração & dosagem
14.
Sex Transm Infect ; 94(7): 508-514, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29907624

RESUMO

OBJECTIVES: Rectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT). METHODS: From 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson's χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted. RESULTS: Of 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. CONCLUSION: Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.


Assuntos
Infecções por Chlamydia/epidemiologia , Enema/estatística & dados numéricos , Gonorreia/epidemiologia , Profilaxia Pré-Exposição/estatística & dados numéricos , Reto/microbiologia , Irrigação Terapêutica/estatística & dados numéricos , Adulto , Chlamydia/isolamento & purificação , Infecções por Chlamydia/prevenção & controle , Estudos de Coortes , Enema/efeitos adversos , Gonorreia/prevenção & controle , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retais/epidemiologia , Doenças Retais/microbiologia , Doenças Retais/prevenção & controle , Reto/efeitos dos fármacos , Assunção de Riscos , Comportamento Sexual , Parceiros Sexuais , Irrigação Terapêutica/efeitos adversos , Adulto Jovem
15.
Clin Infect Dis ; 66(10): 1566-1572, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29228144

RESUMO

Background: Adherence is critical for efficacy of tenofovir disoproxil fumarate/emtricitabine (FTC) as preexposure prophylaxis (PrEP). Methods: Between February 2013 and February 2016, 398 men who have sex with men and transgender women were randomized 1:1 to receive individualized texting for adherence building (iTAB) or standard care (SoC) for 48 weeks. The primary endpoint was dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations at both week 12 and the last on-drug visit of >719 fmol/punch (ie, adequate adherence). Secondary outcomes included DBS TFV-DP concentrations of >1246 fmol/punch (ie, near-perfect adherence) and plasma FTC >350 ng/mL (consistent with dosing within the past 24 hours). Results: Concentrations >719 fmol/punch of TFV-DP were found in 88.6% of participants at week 12 and 82.5% at week 48. For the primary endpoint, the study arms did not differ (72.0% in iTAB and 69.2% in SoC; P > .05). For the secondary composite endpoint of >1246 fmol/punch the iTAB arm was superior to SoC (33.5% vs 24.8%; P = .06), reaching statistical significance when adjusting for age (odds ratio, 1.56 [95% confidence interval, 1.00-2.42]; P < .05). At week 48, iTAB was superior to SoC for near-perfect adherence (51.0% vs 37.4%; P = .02). At week 12, iTAB was superior to SoC for dosing in past 24 hours by plasma FTC (47.5% vs 33.3%; P = .007), but not at weeks 24, 36, and 48 (all P > .05). Conclusions: Automated text messaging is a low-burden tool that improves durability of near-perfect PrEP adherence. Clinical Trials Registration: NCT01761643.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Adesão à Medicação , Organofosfatos/uso terapêutico , Profilaxia Pré-Exposição , Adenina/administração & dosagem , Adenina/sangue , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Humanos , Masculino , Organofosfatos/administração & dosagem , Organofosfatos/sangue , Mensagem de Texto , Pessoas Transgênero
16.
Sex Transm Dis ; 44(4): 211-218, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28282646

RESUMO

The goal of the point-of-care (POC) sexually transmitted infection (STI) Diagnostics meeting was to review the state-of-the-art research and develop recommendations for the use of POC STI diagnostics. Experts from academia, government, nonprofit, and industry discussed POC diagnostics for STIs such as Chlamydia trachomatis, human papillomavirus, Neisseria gonorrhoeae, Trichomonas vaginalis, and Treponema pallidum. Key objectives included a review of current and emerging technologies, clinical and public health benefits, POC STI diagnostics in developing countries, regulatory considerations, and future areas of development. Key points of the meeting are as follows: (i) although some rapid point-of-care tests are affordable, sensitive, specific, easy to perform, and deliverable to those who need them for select sexually transmitted infections, implementation barriers exist at the device, patient, provider, and health system levels; (ii) further investment in research and development of point-of-care tests for sexually transmitted infections is needed, and new technologies can be used to improve diagnostic testing, test uptake, and treatment; (iii) efficient deployment of self-testing in supervised (ie, pharmacies, clinics, and so on) and/or unsupervised (ie, home, offices, and so on) settings could facilitate more screening and diagnosis that will reduce the burden of sexually transmitted infections; (iv) development of novel diagnostic technologies has outpaced the generation of guidance tools and documents issued by regulatory agencies; and (v) questions regarding quality management are emerging including the mechanism by which poor-performing diagnostics are removed from the market and quality assurance of self-testing is ensured.


Assuntos
Testes Imediatos/tendências , Doenças Sexualmente Transmissíveis/diagnóstico , Congressos como Assunto , Humanos , Saúde Pública/métodos
17.
Clin Infect Dis ; 64(4): 428-434, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28174909

RESUMO

Background: Multiple viruses coinfect the male genital tract, influencing each other's replication and perhaps affecting human immunodeficiency virus (HIV) pathogenesis and disease progression. Methods: This study included 453 longitudinal seminal samples from 195 HIV-infected men from the San Diego Primary Infection Resource Consortium and 67 seminal samples from HIV-negative healthy controls. Seminal HIV RNA and DNA from 7 human herpesviruses (HHVs) were measured by real-time polymerase chain reaction. Longitudinal shedding rates were determined by Kaplan-Meier survival analysis. Predictors of viral shedding were determined using backwards selection in a multivariable generalized estimating equation model. Results: HIV-infected participants presented significantly increased rates of seminal HHV shedding compared with HIV-uninfected controls. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were the most commonly detected HHV in semen of HIV-infected participants. Persistent shedding was more common for CMV and EBV when compared to other HHVs. With exception of HHV-7, HHV shedding was not significantly influenced by HIV RNA levels, CD4+ cell counts, or antiretroviral therapy. Presence of CMV, EBV, and herpes simplex virus (HSV) were independent predictors of genital HIV RNA shedding after adjusting for plasma HIV RNA and longitudinal measurements. Conclusions: Seminal replication of multiple HHVs is common in our HIV primary infection cohort. Genital replication of CMV and EBV was the most common and was significantly associated with seminal HIV RNA shedding. Prevalence of HSV shedding was lower and mostly intermittent, but its association with seminal HIV RNA was the strongest. Understanding the complex viral milieu in semen is important for HIV transmission but might also play a role in HIV pathogenesis and disease progression.


Assuntos
Infecções por HIV/virologia , HIV-1 , Sêmen/virologia , Carga Viral , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Coinfecção , DNA Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por Herpesviridae/virologia , Homossexualidade Masculina , Humanos , Estudos Longitudinais , Masculino , RNA Viral , Fatores de Risco , Eliminação de Partículas Virais
18.
AIDS Care ; 29(8): 1014-1018, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28114789

RESUMO

This study evaluated opt-out inpatient HIV screening delivered by admitting physicians, and compared number of HIV tests and diagnoses to signs and symptoms-directed HIV testing (based on physician orders) in the emergency department (ED). The opt-out inpatient HIV screening program was conducted over a one year period in patients who were admitted to the 386-bed University of California San Diego (UCSD) teaching hospital. Numbers of HIV tests and diagnoses were compared to those observed among ED patients who underwent physician-directed HIV testing during the same time period. Survey data were collected from a convenience sample of patients and providers regarding the opt-out testing program. Among 8488 eligible inpatients, opt-out HIV testing was offered to 3017 (36%) patients, and rapid antibody testing was performed in 1389 (16.4%) inpatients, resulting in 6 (0.4% of all tests) newly identified HIV infections (5/6 were admitted through the ED). Among 27,893 ED patients, rapid antibody testing was performed in 88 (0.3%), with 7 (8.0% of all tests) new HIV infections identified. HIV diagnoses in the ED were more likely to be men who have sex with men (MSM) (p = 0.029) and tended to have AIDS-related opportunistic infections (p = 0.103) when compared to HIV diagnoses among inpatients. While 85% of the 150 physicians who completed the survey were aware of the HIV opt-out screening program, 44% of physicians felt that they did not have adequate time to consent patients for the program, and only 30% agreed that a physician is best-suited to consent patients. In conclusion, the yield of opt-out HIV rapid antibody screening in inpatients was comparable to the national HIV prevalence average. However, uptake of screening was markedly limited in this setting where opt-out screening was delivered by physicians during routine care, with limited time resources being the major barrier.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Infecções por HIV/diagnóstico , Pacientes Internados/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , California/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Hospitais de Ensino , Humanos , Pacientes Internados/psicologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Prevalência , Avaliação de Programas e Projetos de Saúde , População Urbana
19.
Sci Rep ; 6: 32947, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27597312

RESUMO

Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Seguimentos , Infecções por HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
20.
Cell Stem Cell ; 19(5): 599-612, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27570067

RESUMO

Age-related human hematopoietic stem cell (HSC) exhaustion and myeloid-lineage skewing promote oncogenic transformation of hematopoietic progenitor cells into therapy-resistant leukemia stem cells (LSCs) in secondary acute myeloid leukemia (AML). While acquisition of clonal DNA mutations has been linked to increased rates of secondary AML for individuals older than 60 years, the contribution of RNA processing alterations to human hematopoietic stem and progenitor aging and LSC generation remains unclear. Comprehensive RNA sequencing and splice-isoform-specific PCR uncovered characteristic RNA splice isoform expression patterns that distinguished normal young and aged human stem and progenitor cells (HSPCs) from malignant myelodysplastic syndrome (MDS) and AML progenitors. In splicing reporter assays and pre-clinical patient-derived AML models, treatment with a pharmacologic splicing modulator, 17S-FD-895, reversed pro-survival splice isoform switching and significantly impaired LSC maintenance. Therapeutic splicing modulation, together with monitoring splice isoform biomarkers of healthy HSPC aging versus LSC generation, may be employed safely and effectively to prevent relapse, the leading cause of leukemia-related mortality.


Assuntos
Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Processamento de RNA/genética , Animais , Sobrevivência Celular/genética , Senescência Celular/genética , Técnicas de Cocultura , Células HEK293 , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Humanos , Camundongos , Síndromes Mielodisplásicas/patologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Spliceossomos/metabolismo , Células Estromais/metabolismo
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