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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hybrid immunity is more protective than vaccination or previous infection alone. To investigate the kinetics of spike-reactive T (TS) cells from SARS-CoV-2 infection through messenger RNA vaccination in persons with hybrid immunity, we identified the T cell receptor (TCR) sequences of thousands of index TS cells and tracked their frequency in bulk TCRß repertoires sampled longitudinally from the peripheral blood of persons who had recovered from coronavirus disease 2019 (COVID-19). Vaccinations led to large expansions in memory TS cell clonotypes, most of which were CD8+ T cells, while also eliciting diverse TS cell clonotypes not observed before vaccination. TCR sequence similarity clustering identified public CD8+ and CD4+ TCR motifs associated with spike (S) specificity. Synthesis of longitudinal bulk ex vivo single-chain TCRß repertoires and paired-chain TCRÉß sequences from droplet sequencing of TS cells provides a roadmap for the rapid assessment of T cell responses to vaccines and emerging pathogens.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Linfocitos T CD8-positivos , Vacunación , ARN Mensajero/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Anticuerpos AntiviralesRESUMEN
BACKGROUND: The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. We hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, we investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons. METHODS: We conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). RESULTS: Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021). CONCLUSIONS: Our study demonstrated that prior infection with HSV partly protects against HZ.
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Herpes Simple , Herpes Zóster , Herpesvirus Humano 1 , Humanos , Herpes Simple/complicaciones , Herpes Simple/epidemiología , Herpesvirus Humano 3 , Estudios Seroepidemiológicos , Masculino , FemeninoRESUMEN
BACKGROUND: The clinical severity of genital HSV-2 infection varies widely among infected persons with some experiencing frequent genital lesions while others are asymptomatic. The viral genital shedding rate is closely associated with and has been established as a surrogate marker of clinical severity. METHODS: To assess the relationship between viral genetics and shedding, we assembled a set of 145 persons who had the severity of their genital herpes quantified through determination of their HSV genital shedding rate. An HSV-2 sample from each person was sequenced and biallelic variants among these genomes were identified. RESULTS: We found no association between metrics of genome-wide variation in HSV-2 and shedding rate. A viral genome-wide association study (vGWAS) identified the minor alleles of three individual unlinked variants as significantly associated with higher shedding rate (p<8.4x10-5): C44973T (A512T), a non-synonymous variant in UL22 (glycoprotein H); A74534G, a synonymous variant in UL36 (large tegument protein); and T119283C, an intergenic variant. We also found an association between the total number of minor alleles for the significant variants and shedding rate (p=6.6x10-7). CONCLUSIONS: These results add to a growing body of literature for HSV suggesting a connection between viral genetic variation and clinically important phenotypes of infection.
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BACKGROUND: Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. METHODS: Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. RESULTS: We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. CONCLUSIONS: T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.
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Herpes simplex virus (HSV) infections are one of the most common and stigmatized infections of humankind, affecting more than 4 billion people around the world and more than 100 million Americans. Yet, most people do not know their infection status, and antibody testing is not recommended, partly due to poor test performance. Here, we compared the test performance of the Roche Elecsys HSV-1 IgG and HSV-2 IgG, DiaSorin LIAISON HSV-1/2 IgG, and Bio-Rad BioPlex 2200 HSV-1 and HSV-2 IgG assays with the gold-standard HSV western blot in 1,994 persons, including 1,017 persons with PCR or culture-confirmed HSV-1 and/or HSV-2 infection. Across all samples, the Bio-Rad and Roche assays had similar performance metrics with low sensitivity (<85%) but high specificity (>97%) for detecting HSV-1 IgG and both high sensitivity (>97%) and high specificity (>98%) for detecting HSV-2 IgG. The DiaSorin assay had a higher sensitivity (92.1%) but much lower specificity (88.7%) for detecting HSV-1 IgG and comparatively poor sensitivity (94.5%) and specificity (94.2%) for detecting HSV-2 IgG. The DiaSorin assay performed poorly at low-positive index values with 60.9% of DiaSorin HSV-1 results and 20.8% of DiaSorin HSV-2 results with positive index values <3.0 yielding false positive results. Based on an estimated HSV-2 seroprevalence of 12% in the United States, positive predictive values for HSV-2 IgG were 96.1% for Roche, 87.4% for Bio-Rad, and 69.0% for DiaSorin, meaning nearly one of every three positive DiaSorin HSV-2 IgG results would be falsely positive. Further development in HSV antibody diagnostics is needed to provide appropriate patient care.IMPORTANCESerological screening for HSV infections is currently not recommended in part due to the poor performance metrics of widely used commercial HSV-1 and HSV-2 IgG assays. Here, we compare three Food and Drug Administration (FDA)-cleared automated HSV-1 and HSV-2 IgG assays to the gold-standard western blot across nearly 2,000 samples. We find that not all commercially available HSV assays are created equal, with comparably low sensitivities for HSV-1 IgG across platforms and high false positivity rates for DiaSorin on HSV-2 IgG. This study is the first large-scale comparison of performance metrics for the Bio-Rad and Roche assays in over 10 years. Our study confirms that there remains room for improvement in HSV serological diagnostic testing-especially in regard to low sensitivities for HSV-1 IgG detection-and highlights that some previously less-studied assays may have better performance metrics than previously considered typical of commercially available HSV-2 IgG assays.
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Anticuerpos Antivirales , Herpes Simple , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Inmunoglobulina G , Sensibilidad y Especificidad , Humanos , Inmunoglobulina G/sangre , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/inmunología , Herpesvirus Humano 2/aislamiento & purificación , Anticuerpos Antivirales/sangre , Herpes Simple/diagnóstico , Herpes Simple/virología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Automatización de Laboratorios , Niño , Anciano de 80 o más Años , Inmunoensayo/métodos , PreescolarRESUMEN
Herpes simplex virus (HSV) causes chronic infection in the human host, characterized by self-limited episodes of mucosal shedding and lesional disease, with latent infection of neuronal ganglia. The epidemiology of genital herpes has undergone a significant transformation over the past two decades, with the emergence of HSV-1 as a leading cause of first-episode genital herpes in many countries. Though dsDNA viruses are not expected to mutate quickly, it is not yet known to what degree the HSV-1 viral population in a natural host adapts over time, or how often viral population variants are transmitted between hosts. This study provides a comparative genomics analysis for 33 temporally-sampled oral and genital HSV-1 genomes derived from five adult sexual transmission pairs. We found that transmission pairs harbored consensus-level viral genomes with near-complete conservation of nucleotide identity. Examination of within-host minor variants in the viral population revealed both shared and unique patterns of genetic diversity between partners, and between anatomical niches. Additionally, genetic drift was detected from spatiotemporally separated samples in as little as three days. These data expand our prior understanding of the complex interaction between HSV-1 genomics and population dynamics after transmission to new infected persons.
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Herpes Genital , Herpes Simple , Herpesvirus Humano 1 , Adulto , Genitales , Genómica , Herpes Simple/epidemiología , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , HumanosRESUMEN
BACKGROUND: Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV-1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post-transplant) who were not taking daily antiviral suppressive therapy. METHODS: Participants self-collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary. RESULTS: Sample collection adherence was high (median 122 swabs/person, range: 85.7%-101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%-33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8-46.1 hrs). CONCLUSION: Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice-daily sampling may be sufficient to detect most episodes. These data show that self-collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population.
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Herpesvirus Humano 1 , Receptores de Trasplantes , Esparcimiento de Virus , Humanos , Proyectos Piloto , Masculino , Persona de Mediana Edad , Femenino , Receptores de Trasplantes/estadística & datos numéricos , Anciano , Herpesvirus Humano 1/aislamiento & purificación , Adulto , Trasplante de Órganos/efectos adversos , Herpes Simple/virología , Activación Viral , Trasplante de Riñón/efectos adversos , Terapia de Inmunosupresión/efectos adversos , Trasplante de Hígado/efectos adversosRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic.
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COVID-19 , Enfermedades Transmisibles , Humanos , Femenino , Grupos Minoritarios , Pandemias , Docentes MédicosRESUMEN
Class II tetramer reagents for eleven common DR alleles and a DP allele prevalent in the world population were used to identify SARS-CoV-2 CD4+ T cell epitopes. A total of 112, 28 and 42 epitopes specific for Spike, Membrane and Nucleocapsid, respectively, with defined HLA-restriction were identified. Direct ex vivo staining of PBMC with tetramer reagents was used to define immunodominant and subdominant T cell epitopes and estimate the frequencies of these T cells in SARS-CoV-2 exposed and naïve individuals. Majority of SARS-CoV-2 epitopes identified have <67% amino acid sequence identity with endemic coronaviruses and are unlikely to elicit high avidity cross-reactive T cell responses. Four SARS-CoV-2 Spike reactive epitopes, including a DPB1*04:01 restricted epitope, with ≥67% amino acid sequence identity to endemic coronavirus were identified. SARS-CoV-2 T cell lines for three of these epitopes elicited cross-reactive T cell responses to endemic cold viruses. An endemic coronavirus Spike T cell line showed cross-reactivity to the fourth SARS-CoV-2 epitope. Three of the Spike cross-reactive epitopes were subdominant epitopes, while the DPB1*04:01 restricted epitope was a dominant epitope. Frequency analyses showed Spike cross-reactive T cells as detected by tetramers were present at relatively low frequency in unexposed people and only contributed a small proportion of the overall Spike-specific CD4+ T cells in COVID-19 convalescent individuals. In total, these results suggested a very limited number of SARS-CoV-2 T cells as detected by tetramers are capable of recognizing ccCoV with relative high avidity and vice versa. The potentially supportive role of these high avidity cross-reactive T cells in protective immunity against SARS-CoV-2 needs further studies.
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Linfocitos T CD4-Positivos/inmunología , COVID-19/inmunología , Reacciones Cruzadas , SARS-CoV-2/inmunología , COVID-19/epidemiología , Convalecencia , Epítopos , Epítopos de Linfocito T/inmunología , Humanos , Pandemias , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
BACKGROUND: Bacterial vaginosis is a risk factor for sexually transmitted infections, including HIV. Adult African women have a high prevalence of bacterial vaginosis, but it is not known when first bacterial vaginosis occurs. OBJECTIVE: This study aimed to describe bacterial vaginosis in younger African women, before and after first sex, and to determine the incidence of bacterial vaginosis and significant correlates of bacterial vaginosis incidence and recurrence. STUDY DESIGN: In a prospective observational cohort study enrolling adolescents with limited sexual experience, young women aged 16 to 21 years were recruited in Thika, Kenya. Eligible participants were HIV and herpes simplex virus 2 seronegative and reported 0 or 1 lifetime sexual partner. The Nugent score was determined at quarterly visits from vaginal Gram stains. The trends in bacterial vaginosis were described over time; hazard ratios were calculated using Cox regression, and relative risk of bacterial vaginosis was estimated using generalized estimating equations and Poisson regression. RESULTS: A total of 400 participants with a median age of 18.6 years (interquartile range, 16-21) were enrolled. Of note, 322 participants (80.5%) reported no history of sex, whereas 78 participants (19.5%) reported sex with 1 partner. At enrollment, bacterial vaginosis (Nugent score of ≥7) was uncommon (21/375 [5.6%]). Overall, 144 participants had bacterial vaginosis at least once, for an incidence rate of 16.5 cases per 100 person-years. Before first sex, bacterial vaginosis was present at 2.8% of visits, compared with 13.7% of visits after first sex. An adjusted model of bacterial vaginosis incidence observed that first sex was associated with more than a 2-fold increased bacterial vaginosis risk (adjusted hazard ratio, 2.44; 95% confidence interval, 1.25-4.76; P=.009). Chlamydia diagnosis (adjusted hazard ratio, 1.73; 95% confidence interval, 1.1-2.8; P=.02), and herpes simplex virus 2 seropositivity (adjusted hazard ratio, 2.88; 95% confidence interval, 1.17-7.09; P=.021) were both associated with incident bacterial vaginosis. A multivariate generalized estimating equation model, including all episodes of bacterial vaginosis, demonstrated risk factors, including first sex, sexually transmitted infections, urban residence, recent sex, and no income; the most important risk factor was first sex (adjusted relative risk, 1.92; 95% confidence interval, 1.12-3.31; P=.018). The probability of bacterial vaginosis increased with each subsequent episode; mean Nugent scores increased after each bacterial vaginosis episode. CONCLUSION: Using detailed longitudinal observation, this study found that Kenyan adolescents have almost no bacterial vaginosis before first sex and that initiation of sexual activity was the strongest risk factor for both prevalent bacterial vaginosis and incident bacterial vaginosis.
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Infecciones por VIH , Enfermedades de Transmisión Sexual , Vaginosis Bacteriana , Adulto , Femenino , Adolescente , Humanos , Kenia/epidemiología , Incidencia , Estudios Prospectivos , Prevalencia , Enfermedades de Transmisión Sexual/epidemiología , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/complicaciones , Conducta Sexual , Factores de Riesgo , Infecciones por VIH/epidemiología , Infecciones por VIH/complicacionesRESUMEN
BACKGROUND: Adolescent girls and young women (AGYW) have a high incidence of unplanned pregnancies, especially in low-resource settings. AGYW assess the overlapping risks of pregnancy, contraception, and STIs as they navigate relationships. Few studies have examined how AGYW consider the comparative risks of their decisions around sexual and reproductive health in this context or how risk perception influences contraceptive use. METHODS: Twenty in-depth interviews (IDIs) and 5 focus group discussions (FGDs) were conducted with a subset of sexually active AGYW enrolled in the Girls Health Study (GHS), a longitudinal cohort study in Thika, Kenya, assessing HSV-2 incidence in a cohort of AGYW aged 16-20. Interview questions were focused on perspectives and decision-making around sexual and reproductive health. Interviews were conducted in both English and Kiswahili, transcribed, and coded using inductive and deductive approaches to identify emerging themes. RESULTS: Misconceptions about long-acting reversible contraceptives (LARCs), injectables, and daily oral contraceptive pills strongly disincentivized their use among AGYW. Participants described pregnancy as undesirable, and AGYW reported prioritizing contraceptive methods that were effective and reliable in pregnancy prevention, even if not effective in preventing STI/HIV infection. Participants reported that AGYW relied heavily on emergency contraceptive (EC) pills for pregnancy prevention. CONCLUSIONS: Though the goal of avoiding unintended pregnancy was common, this did not suffice to motivate the uptake of long-term contraceptives among AGYWs. Given the convenience, cost-effectiveness, and lower perceived risk of side effects, EC pills were more likely to be accepted as a form of contraception. Understanding the reasons for AGYW's acceptance of certain contraceptive methods over others can help future interventions better target communication and counseling about contraception and influence key drivers of AGYW behavior and decision-making around sexual and reproductive health.
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Infecciones por VIH , Enfermedades de Transmisión Sexual , Embarazo , Humanos , Femenino , Adolescente , Anticonceptivos , Infecciones por VIH/epidemiología , Kenia , Estudios Longitudinales , Enfermedades de Transmisión Sexual/prevención & control , ActitudRESUMEN
While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , Humanos , Cinética , ARN Viral/análisis , ARN Viral/genética , SARS-CoV-2/genética , Carga ViralRESUMEN
Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%-â 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).
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COVID-19 , COVID-19/diagnóstico , Prueba de COVID-19 , Humanos , Estudios Longitudinales , SARS-CoV-2RESUMEN
INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.
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Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Humanos , Hidroxicloroquina/uso terapéutico , Carga ViralRESUMEN
Epstein-Barr virus (EBV) is transmitted by saliva and is a major cause of cancer, particularly in people living with HIV/AIDS. Here, we describe the frequency and quantity of EBV detection in the saliva of Ugandan adults with and without HIV-1 infection and use these data to develop a novel mathematical model of EBV infection in the tonsils. Eligible cohort participants were not taking antiviral medications, and those with HIV-1 infection had a CD4 count >200 cells/mm3. Over a 4-week period, participants provided daily oral swabs that we analysed for the presence and quantity of EBV. Compared with HIV-1 uninfected participants, HIV-1 coinfected participants had an increased risk of EBV detection in their saliva (IRR = 1.27, 95% CI = 1.10-1.47) and higher viral loads in positive samples. We used these data to develop a stochastic, mechanistic mathematical model that describes the dynamics of EBV, infected cells, and immune response within the tonsillar epithelium to analyse potential factors that may cause EBV infection to be more severe in HIV-1 coinfected participants. The model, fit using Approximate Bayesian Computation, showed high fidelity to daily oral shedding data and matched key summary statistics. When evaluating how model parameters differed among participants with and without HIV-1 coinfection, results suggest HIV-1 coinfected individuals have higher rates of B cell reactivation, which can seed new infection in the tonsils and lower rates of an EBV-specific immune response. Subsequently, both these traits may explain higher and more frequent EBV detection in the saliva of HIV-1 coinfected individuals.
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Coinfección/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Infecciones por VIH/complicaciones , VIH-1 , Tonsila Palatina/virología , Adolescente , Adulto , Linfocitos B/inmunología , Estudios de Cohortes , Coinfección/inmunología , Biología Computacional , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Infecciones por VIH/inmunología , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/fisiología , Humanos , Inmunidad Celular , Masculino , Persona de Mediana Edad , Modelos Biológicos , Tonsila Palatina/inmunología , Saliva/virología , Procesos Estocásticos , Uganda , Carga Viral , Esparcimiento de Virus , Adulto JovenRESUMEN
BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.
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Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/prevención & control , Hidroxicloroquina/uso terapéutico , Profilaxis Posexposición , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Método Doble Ciego , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is safe and effective for use in people who inject drugs (PWID), but PrEP is underutilized in this population. We assessed awareness of PrEP and correlates of interest in PrEP among PWID in Seattle, Washington. METHODS: This study analyzed data from a 2019 survey of PWID at 3 Seattle-area syringe service programs (SSPs). We used descriptive statistics to compare PrEP-aware and unaware PWID and multivariable Poisson regression with robust standard errors to estimate adjusted prevalence ratios (APR) for interest in PrEP. RESULTS: Among 348 HIV-negative PWID, ≤1% were currently taking PrEP, 51% were PrEP aware and 46% were interested in PrEP. Interest in PrEP was inversely associated with prior PrEP awareness (APR 0.58, 95% CI 0.45 - 0.74); however, interest in PrEP was high among PWID meeting pre-specified risk criteria for HIV (APR 1.41, 95% CI 1.06 - 1.88). CONCLUSIONS: Our results suggest increasing awareness of PrEP may not be sufficient to promote PrEP uptake among PWID, and further efforts are needed to understand perceptions of risk for HIV, determinants of PrEP use, and to investigate successful strategies for PrEP implementation and delivery in this marginalized population.Supplemental data for this article is available online at https://doi.org/10.1080/10826084.2021.2012688 .
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Infecciones por VIH , Seropositividad para VIH , Profilaxis Pre-Exposición , Abuso de Sustancias por Vía Intravenosa , Infecciones por VIH/epidemiología , Humanos , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa/epidemiología , Jeringas , WashingtónRESUMEN
Background: Substance use-related diagnoses are common and associated with poor health outcomes. The objective of this analysis was to compare rates of cervical cancer screening, screening abnormalities, and follow-up care in women with and without a substance use-related diagnosis seen for primary care between January 1, 2016 and December 31, 2019 in the University of Washington healthcare system. Methods: This study included women aged 21-65 years of age who had at least one outpatient visit between January 1, 2016 and December 31, 2019 within one of 45 primary care or women's health clinics in the academic healthcare system. Exposure status was defined using ICD10 codes for substance-use related diagnoses or no substance-use related diagnoses. Only first cervical cancer screening was included. Generalized linear models with a binomial family and log link were used to estimate risk ratios. Results: 3845 women had a substance use-related diagnosis and 89214 did not. Women with a substance use-related diagnosis were less likely to be screened for cervical cancer (44%, 1675/3845) compared to women without a substance use-related diagnosis (49%, 43338/89214; relative risk [RR] 0.90, 95% CI 0.86-0.93). Women with a substance use-related diagnosis were also more likely to have an abnormal screening result (18%, 304/1675) compared to women without a substance use-related diagnosis (10%, 4528/43338; RR 1.74, 95% CI 1.56-1.93). Follow-up for abnormal screens did not differ significantly between groups (24 vs 25%; RR 0.80, 95% CI 0.55-1.17). Conclusion: To combat disparities in cervical cancer screening for women with substance use-related diagnoses, public health efforts should expand access to screening where women with substance use-related diagnoses are seen, including acute care, inpatient hospitalizations, and addiction treatment settings.
Asunto(s)
Trastornos Relacionados con Sustancias , Neoplasias del Cuello Uterino , Adulto , Anciano , Detección Precoz del Cáncer , Femenino , Estudios de Seguimiento , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Adulto JovenRESUMEN
Importance: Herpes simplex virus type 1 (HSV-1) is the leading cause of first-episode genital herpes in many countries. Objective: To inform counseling messages regarding genital HSV-1 transmission, oral and genital viral shedding patterns among persons with first-episode genital HSV-1 infection were assessed. The trajectory of the development of HSV-specific antibody and T-cell responses was also characterized. Design, Setting, and Participants: Prospective cohort followed up for up to 2 years, with 82 participants followed up between 2013 and 2018. Participants were recruited from sexual health and primary care clinics in Seattle, Washington. Persons with laboratory-documented first-episode genital HSV-1 infection, without HIV infection or current pregnancy, were referred for enrollment. Exposures: First-episode genital HSV-1 infection. Main Outcomes and Measures: Genital and oral HSV-1 shedding and lesion rates at 2 months, 11 months, and up to 2 years after initial genital HSV-1 infection. Participants self-collected oral and genital swabs for HSV polymerase chain reaction testing for 30 days at 2 and 11 months and up to 2 years after diagnosis of genital HSV-1. Blood samples were collected at serial time points to assess immune responses to HSV-1. Primary HSV-1 infection was defined as absent HSV antibody at baseline or evolving antibody profile using the University of Washington HSV Western Blot. HSV-specific T-cell responses were detected using interferon γ enzyme-linked immunospot. Results: Among the 82 participants, the median (range) age was 26 (16-64) years, 54 (65.9%) were women, and 42 (51.2%) had primary HSV-1 infection. At 2 months, HSV-1 was detected from the genital tract in 53 participants (64.6%) and in the mouth in 24 participants (29.3%). Genital HSV-1 shedding was detected on 275 of 2264 days (12.1%) at 2 months and declined significantly to 122 of 1719 days (7.1%) at 11 months (model-predicted rate, 6.2% [95% CI, 4.3%-8.9%] at 2 months vs 3.2% [95% CI, 1.8%-5.7%] at 11 months; relative risk, 0.52 [95% CI, 0.29-0.93]). Genital lesions were rare, reported on 65 of 2497 days (2.6%) at 2 months and 72 of 1872 days (3.8%) at 11 months. Oral HSV-1 shedding was detected on 88 of 2247 days (3.9%) at 2 months. Persons with primary HSV-1 infection had a higher risk of genital shedding compared with those with nonprimary infection (model-predicted rate, 7.9% [95% CI, 5.4%-11.7%] vs 2.9% [95% CI, 1.7%-5.0%]; relative risk, 2.75 [95% CI, 1.40-5.44]). Polyfunctional HSV-specific CD4+ and CD8+ T-cell responses were maintained during the follow-up period. Conclusions and Relevance: Genital HSV-1 shedding was frequent after first-episode genital HSV-1, particularly among those with primary infection, and declined rapidly during the first year after infection.