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BACKGROUND: On-demand topical products could be an important tool for HIV prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG; 16 mg/20 mg) insert administered rectally. METHODS: MTN-039 was a Phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid (RF), and rectal tissue (RT) were collected over 72 hours (hr) following rectal administration of one and two TAF/EVG inserts for each participant. ClinicalTrials.gov Identifier: NCT04047420. RESULTS: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. RT EVG peaked at 2-hr (median 2 inserts= 9 ng/mg) but declined to BLQ in the majority of samples at 24-hr, whereas TFV-DP remained high >2,000 fmol/million cells for 72-hr with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each timepoint for both 1 and 2 inserts (p<0.065 and p<0.039, respectively). DISCUSSION: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours.
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We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998-2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p < .001). Associations among MSM without HIV were similar, with average marijuana use (r = .19) and stimulant use (r = .22) being positively correlated with average ED drug use, and were also correlated with having multiple partners (r = .36), insertive anal intercourse with condom (r = .22), and insertive anal intercourse without condom (r = .18) over time. Positive within-individual associations between ED drug use and multiple partners and insertive anal intercourse with and without condom were observed regardless of HIV serostatus. This study showed that MSM who reported use of ED drugs were also, on average, more likely to use recreational drugs and engage in sexual activities, such as having multiple partners and insertive anal intercourse. Within individuals, average ED drug use was also positively correlated with sexual behaviors.
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Disfunción Eréctil , Preparaciones Farmacéuticas , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Estudios de Cohortes , Disfunción Eréctil/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Conducta Sexual , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
Rationale: Mechanisms of HIV-associated chronic obstructive pulmonary disease (COPD) are poorly understood. The oral microbiome shapes the lung microbiome, and gut dysbiosis can affect lung diseases; however, relationships of the oral and gut microbiome to COPD in HIV have not been explored.Objectives: To examine alterations in the oral and gut microbiome associated with pulmonary disease in persons with HIV (PWH).Methods: Seventy-five PWH and 93 HIV-uninfected men from the MACS (Multicenter AIDS Cohort Study) performed pulmonary function testing. Sequencing of bacterial 16S ribosomal RNA in saliva and stool was performed. We used nonmetric multidimensional scaling, permutational multivariate ANOVA, and linear discriminant analysis to analyze communities by HIV and lung function.Measurements and Main Results: Oral microbiome composition differed by HIV and smoking status. Alterations of oral microbial communities were observed in PWH with abnormal lung function with increases in relative abundance of Veillonella, Streptococcus, and Lactobacillus. There were no significant associations between the oral microbiome and lung function in HIV-uninfected individuals. No associations with HIV status or lung function were seen with the gut microbiome.Conclusions: Alterations of oral microbiota in PWH were related to impaired pulmonary function and to systemic inflammation. These results suggest that the oral microbiome may serve as a biomarker of lung function in HIV and that its disruption may contribute to COPD pathogenesis.
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Microbioma Gastrointestinal , Infecciones por VIH/complicaciones , Infecciones por VIH/microbiología , Microbiota , Boca/microbiología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVES: We sought to calculate HIV incidence in a retrospective cohort of young (13-29â years old) black men who have sex with men (YBMSM) accessing repeated HIV-antibody testing in a mid-size city in the USA. METHODS: We aggregated site-specific HIV-antibody testing results from the project's inception among YBMSM who received an initial negative result and accessed at least one additional HIV-antibody test. From these data, we assessed number of seroconversions and person-years and calculated HIV incidence using a mid-P exact test to estimate 95% CIs. RESULTS: Five seroconversions were documented over 42.3 person-years (the mean age at first onsite test: 19.7â years), resulting in an HIV incidence rate of 11.8% (95% CI 4.3% to 26.2%). The mean age at seroconversion was 20.4 (±3.0)â years. CONCLUSIONS: Even in mid-size cities with low HIV prevalence rates in the general population, HIV incidence among YBMSM may be high. Community-based HIV-antibody testing organisations serving YBMSM should be encouraged and trained to track repeated HIV testing and calculate HIV incidence rates. Increased resources should be deployed to develop and encourage regular HIV testing in community health sites serving YBMSM.
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Negro o Afroamericano/estadística & datos numéricos , Infecciones por VIH/etnología , Homosexualidad Masculina/estadística & datos numéricos , Adolescente , Adulto , Seropositividad para VIH/etnología , Homosexualidad Masculina/etnología , Humanos , Incidencia , Masculino , Pennsylvania/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods: MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results: MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions: Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218.
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Infecciones por VIH/tratamiento farmacológico , Recto/efectos de los fármacos , Recto/virología , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Tenofovir/administración & dosificación , Adolescente , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Geles , Glicerol , Infecciones por VIH/virología , VIH-1 , Homosexualidad Masculina , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/efectos adversos , Tenofovir/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To assess the efficacy of topical 80% trichloroacetic acid (TCA) to treat internal anal high-grade squamous intraepithelial lesions (HSILs) in HIV-positive individuals. METHODS: All patients who attended the University of Pittsburgh Anal Dysplasia Clinic for treatment of biopsy-proven internal anal HSIL with topical TCA between July 1, 2009, and June 30, 2012, and who had 1 or more follow-up visits to assess treatment efficacy were included in the analysis. Recurrence of HSIL was assessed in July 1, 2013. RESULTS: A total of 98 HSILs from 72 patients were treated, and 77 (78.6%) resolved to normal epithelium or low-grade SIL during follow-up. Forty-eight (49.0%) and 27 (27.6%) of lesions resolved with 1 and 2 TCA treatments, respectively, whereas 1 lesion (1%) each resolved with 3 and 4 TCA treatments. Twenty-one (21.4%) lesions in 20 patients remained without resolution after TCA treatments. These patients were offered an alternative treatment. During follow-up, 8 (15.1%) of 53 patients had a lesion that recurred at the index site (11/53 [20.8%], inclusive of adjacent lesions) and 17 patients had new lesions diagnosed. CONCLUSIONS: Topical TCA is an efficacious treatment of internal anal HSIL in an anal dysplasia clinic setting with high-resolution anoscopy capacity. Advantages of TCA for this recurrent disease process include the following: low cost, no requirement for special equipment beyond that for high-resolution anoscopy, and painless application procedure. A larger prospective comparative study would better define efficacy and patient acceptability between treatment methods.
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Canal Anal/patología , Neoplasias del Ano/prevención & control , Carcinoma de Células Escamosas/prevención & control , Cáusticos/uso terapéutico , Seropositividad para VIH/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/tratamiento farmacológico , Ácido Tricloroacético/uso terapéutico , Administración Tópica , Adulto , Anciano , Canal Anal/inmunología , Neoplasias del Ano/patología , Carcinoma de Células Escamosas/patología , Cáusticos/administración & dosificación , Femenino , Estudios de Seguimiento , Seropositividad para VIH/inmunología , Humanos , Masculino , Tamizaje Masivo , Salud del Hombre , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Proctoscopía , Estudios Retrospectivos , Lesiones Intraepiteliales Escamosas de Cuello Uterino/inmunología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/patología , Lesiones Intraepiteliales Escamosas de Cuello Uterino/prevención & control , Resultado del Tratamiento , Ácido Tricloroacético/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH). DESIGN: Cross-sectional. METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score). RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had one or more vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers. CONCLUSIONS: Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH. CLINICAL TRIALS REGISTRATION: NCT02344290.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Infecciones por VIH , Placa Aterosclerótica , Femenino , Masculino , Humanos , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Estudios Transversales , Infecciones por VIH/complicaciones , Biomarcadores , Placa Aterosclerótica/diagnóstico por imagenRESUMEN
BACKGROUND: Hepatic steatosis, including nonalcoholic fatty liver disease (NAFLD), is common among people with HIV (PWH). We present baseline steatosis prevalence and cardiometabolic characteristics among REPRIEVE substudy participants. METHODS: REPRIEVE is an international, primary cardiovascular disease prevention, randomized, controlled trial of pitavastatin calcium vs. placebo among 7769 PWH ages 40-75âyears on antiretroviral therapy (ART) and with low-to-moderate cardiovascular risk. A subset of participants underwent noncontrast computed tomography, with hepatic steatosis defined as mean hepatic attenuation less than 40 HU or liver/spleen ratio less than 1.0, and NAFLD defined as steatosis in the absence of frequent alcohol use or viral hepatitis. RESULTS: Of 687 evaluable persons, median age was 51âyears, BMI 27âkg/m 2 , CD4 + T-cell count 607 cells/µl; 17% natal female sex, 36% Black, 24% Hispanic, and 98% HIV-1 RNA less than 400âcopies/ml. Hepatic steatosis prevalence was 22% (149/687), and NAFLD 21% (96/466). Steatosis/NAFLD prevalence was higher in men and with older age, non-Black race, and higher BMI and waist circumference. Both were associated with BMI greater than 30âkg/m 2 , metabolic syndrome components, higher atherosclerotic cardiovascular disease (ASCVD) risk score, HOMA-IR, LpPLA-2 and hs-CRP, and lower high-density lipoprotein cholesterol. Of HIV-specific/ART-specific characteristics, only history of an AIDS-defining illness was more common among persons with steatosis/NAFLD. After adjusting for age, sex and race/ethnicity, BMI greater than 30âkg/m 2 , HOMA-IR greater than 2.0, Metabolic syndrome and each of its components were associated with NAFLD prevalence. CONCLUSION: In this cohort with controlled HIV and low-to-moderate cardiovascular risk, hepatic steatosis and NAFLD were common and associated with clinically relevant metabolic and inflammatory disturbances but not current HIV-related or ART-related factors.
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Enfermedades Cardiovasculares , Infecciones por VIH , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Prevención Primaria , Adulto , AncianoRESUMEN
Objective: Examine prospective relationships between erectile dysfunction (ED) drugs EDand CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM). Methods: Data from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semi-annual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation was fitted to estimate the mean differences for the effects of self-reported ED drug use on CD4 and CD8 T-cell outcomes and immune biomarkers. Results: Total of 1,391 men with HIV (MWH) and 307 men without HIV (MWOH) was included. Baseline mean CD4 cell count among MWH and MWOH was 499.9 cells/µL and 966.7 cells/µL, respectively. At baseline, 41.8% of MWH were virally suppressed. ED drug users reported a mean of 44.4 months of exposure to ED drugs. ED drug use was associated with increased CD4 cell outcomes among MWH but not MWOH. Mean differences in CD4 cell counts after 1 year of ED drug use was 57.6 cells/µL and increased to 117.7 after 10 years among MWH. CD8 counts were higher in ED drug users among MWH over 10 years than non-users; no consistent differences were found among MWOH. ED drug use appeared to reduce immune marker levels, such as IL-6 and increase markers, such as IL-10. We observed similar effects of ED drug use on biomarker levels among MWOH. Conclusion: Long-term use of ED drugs do not adversely affect immune function among MWH or MWOH. Future studies on the relationships between different types of ED drugs and effects on T-cell subtypes are warranted.
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Peptostreptococcus infective endocarditis is rare but associated with high morbidity. We report two cases and evaluate all positive blood cultures for Peptostreptococcus at our institution, followed by a review of the literature. This organism causes a subacute presentation and cardiac valve pathology is a risk factor. Penicillin remains the treatment of choice.
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Bacteriemia/diagnóstico , Endocarditis/diagnóstico , Infecciones por Bacterias Grampositivas/diagnóstico , Peptostreptococcus/aislamiento & purificación , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/patología , Ecocardiografía , Endocarditis/tratamiento farmacológico , Endocarditis/microbiología , Endocarditis/patología , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/patología , Válvulas Cardíacas/patología , Hospitales , Humanos , Incidencia , Persona de Mediana Edad , Penicilinas/uso terapéuticoRESUMEN
Candida rugosa is a rare cause of candidaemia, but important to recognize because of frequent azole-resistance and its association with catheters and total parenteral nutrition. Recommended therapy is an echinocandin or amphotericin, and catheter discontinuation. Fluconazole might be substituted based on susceptibility testing and a clinical response to initial therapy.