Impact of Dietary Quality on Genital Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Most cervical cancers are directly linked to oncogenic or high-risk human papillomavirus (HR-HPV) infection. This study evaluates associations between diet quality and genital HPV infection in women. METHODS: This study included 10 543 women from the 2003-2016 National Health and Nutrition Examination Survey. The outcome was the genital HPV infection status (HPV-negative, low-risk [LR] HPV, and HR-HPV). Dietary quality was evaluated using the Healthy Eating Index (HEI), in which a higher score indicates a better diet quality. RESULTS: Women who did not consume total fruits (15.8%), whole fruits (27.5%), or green vegetables and beans (43%) had a significantly higher risk of HR-HPV infection than women who complied with the Dietary Guidelines for Americans (HR-HPV odds ratio = 1.76, 1.63, and 1.48 for a HEI score of 0 vs 5, respectively) after adjusting confounding factors. Similar results of these food components on LR-HPV infection were found. In addition, intake of whole grains and dairy was inversely associated with LR-HPV infection. CONCLUSIONS: This study showed that women who did not eat fruits, dark-green vegetables, and beans had a higher risk of genital HR-HPV infection. Intake of these food components is suggested for women to prevent HPV carcinogenesis.

Longitudinal Variations in Antibody Responses against SARS-CoV-2 Spike Epitopes upon Serial Vaccinations.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted healthcare, the workforce, and worldwide socioeconomics. Multi-dose mono- or bivalent mRNA vaccine regimens have shown high efficacy in protection against SARS-CoV-2 and its emerging variants with varying degrees of efficacy. Amino acid changes, primarily in the receptor-binding domain (RBD), result in selection for viral infectivity, disease severity, and immune evasion. Therefore, many studies have centered around neutralizing antibodies that target the RBD and their generation achieved through infection or vaccination. Here, we conducted a unique longitudinal study, analyzing the effects of a three-dose mRNA vaccine regimen exclusively using the monovalent BNT162b2 (Pfizer/BioNTech) vaccine, systematically administered to nine previously uninfected (naïve) individuals. We compare changes in humoral antibody responses across the entire SARS-CoV-2 spike glycoprotein (S) using a high-throughput phage display technique (VirScan). Our data demonstrate that two doses of vaccination alone can achieve the broadest and highest magnitudes of anti-S response. Moreover, we present evidence of novel highly boosted non-RBD epitopes that strongly correlate with neutralization and recapitulate independent findings. These vaccine-boosted epitopes could facilitate multi-valent vaccine development and drug discovery.

Antioxidants Associated With Oncogenic Human Papillomavirus Infection in Women.

BACKGROUND: Human papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed the onset of HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The association between antioxidants and oncogenic HPV remains unclear. In this study, we aim to identify antioxidants associated with vaginal HPV infection in women. METHODS: The associations between the 15 antioxidants and vaginal HPV infection status (no, low-risk [LR], and high-risk [HR] HPV) were evaluated using 11 070 women who participated in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). RESULTS: We identified serum albumin and 4 dietary antioxidants (vitamin A, B2, E, and folate) inversely associated with HR-HPV infection. Women with a low level of albumin (≤39 g/L) have a significantly higher risk of HR-HPV (odds ratio [OR] = 1.4, P = .009 vs >44 g/L). A Nutritional Antioxidant Score (NAS) was developed based on these 4 dietary antioxidants. The women with the lowest quartile NAS had a higher chance of HR-HPV (OR = 1.3, P = .030) and LR-HPV (OR = 1.4, P = .002) compared with the women with the highest quartile NAS. CONCLUSIONS: We identified 5 antioxidants negatively associated with vaginal HR-HPV infection in women. Our findings provide valuable insights into understanding antioxidants' impact on HPV carcinogenesis.

Risk of abnormal cervical cytology in HIV-infected women testing positive for both human papillomavirus and Epstein-Barr virus in genital tract specimens.

PURPOSE: Although infection with high-risk human papillomavirus (HPV) is a prerequisite for cervical cancer development, HPV infection is not sufficient to promote cancer in the majority of infected women. We tested the hypothesis that human herpesviruses might cooperate with HPV to promote the development of cervical dysplasia, an early indicator of cervical cancer development. METHODS: This study used archived specimens from a cohort of human immunodeficiency virus (HIV)-seropositive women seeking gynecological care at the Medical Center of New Orleans, Louisiana. Viral DNA was detected by PCR amplification and risk of abnormal cervical cytology was determined in relation to virus test results. RESULTS: Consensus human herpesvirus PCR with herpes speciation by restriction endonuclease digestion revealed Epstein-Barr virus (EBV) to be the most prevalent herpesvirus in cervicovaginal lavage specimens. Further analysis using an EBV-specific PCR assay and cervical swab specimens demonstrated an approximately fourfold increased risk of abnormal cervical cytology in women testing positive for cervical EBV and high-risk HPV compared to women testing positive for high-risk HPV alone. This relationship was independent of markers of advancing HIV disease. CONCLUSION: Cervical shedding of EBV appears to predict a greater risk of cervical dysplasia in HIV-infected women with a high-risk HPV infection.

Interplay between oral immunity in HIV and the microbiome.

This Basic Science Workshop addressed the oral microbiome. At the 7th World Workshop on Oral Health & Disease in HIV/AIDS in India in 2014, some aspects of the human microbiome were discussed, and research questions formulated. Since that time, there have been major advances in technology, which have stimulated a number of publications on many aspects of the human microbiome, including the oral cavity. This workshop aimed to summarize current understanding of the "normal" microbiome of the oral cavity compared to that during HIV infection, and how oral immune factors and other clinical variables alter or control the oral microbiome. An important question is whether successful treatment with anti-retroviral therapy, which leads to a significant drop in viral loads and immune reconstitution, is associated with any change or recovery of the oral microbiome. Additionally, the workshop addressed the issue of which parameters are most appropriate/correct to evaluate the oral microbiome and how clinically relevant are shifts/changes in the oral microbiome. The workshop evaluated current knowledge in five research areas related to five basic questions and identified further topics where further research is required.

Cervical Human Papillomavirus Testing With Two Home Self-Collection Methods Compared With a Standard Clinically Collected Sampling Method.

BACKGROUND: The purpose of this study was to compare the outcomes of 2 self-collection methods to detect cervical human papillomavirus (HPV) DNA with outcomes from a standard clinical method. The standard method samples were collected by a clinician at a routine pelvic examination. Self-samples were taken at home and mailed to the clinical laboratory. METHODS: The 2 self-collection methods were a tampon-based method and a swab-based method using a commercial device, an Eve Medical HerSwab. All HPV samples were processed by a clinical laboratory using the Food and Drugs Administration approved Roche Cobase HPV method, which specifically identifies HPV 16, HPV 18, and a set of 12 other high-risk subtypes. Patients were recruited from 2 cancer screening clinics 2015 to 2017. All patients signed an informed consent. Screening outcomes, such as prevalence, percent agreement with standard, sensitivity, and specificity, were calculated for each self-collection method. Measures of similarity between self and standard collection outcomes, Cohen's κ, percent concordance, McNemar equivalence, and others were tested statistically. RESULTS: One hundred seventy-four patients were randomized. The prevalence of 1 or more positive HPV high-risk subtypes from the standard clinical specimens was 13.5%. All clinical specimens were sufficient for valid HPV detection. For the tampon method, 15 (27%) of the specimens were insufficient quality. Only 1 (2%) swab specimen was insufficient. Only the swab self-collection method was found to be statistically noninferior to the clinical method. The tampon method had an unacceptably high rate of insufficient quality specimens and also failed the equivalency tests. CONCLUSIONS: The swab home collection samples were equivalent to the clinical samples, but the tampon method had an unacceptably high rate of specimens insufficient for HPV detection.

Epstein-Barr Virus, High-Risk Human Papillomavirus and Abnormal Cervical Cytology in a Prospective Cohort of African Female Sex Workers.

BACKGROUND: High-oncogenic-risk human papillomavirus (hrHPV) is necessary, although insufficient, to promote cervical cancer. Like HPV, Epstein-Barr virus (EBV) is a common pathogen with the capacity to promote epithelial neoplasms. We examined the association between cervical EBV, hrHPV, and cytology in female sex workers in Nairobi, Kenya. METHODS: Women (n = 332) with known cervical cytology and hrHPV mRNA results were evaluated for cervical EBV DNA by conventional polymerase chain reaction. Prevalence ratios (PRs) were calculated to assess the relationships between EBV, hrHPV, and cervical cytology. Prospective analyses used risk ratios and time-to-event analyses to determine the association of EBV with hrHPV clearance and with abnormal cytology outcomes. RESULTS: Baseline prevalence of hrHPV and EBV was 29% and 19%, respectively. Higher EBV prevalence was found among women with older age, HIV, hrHPV, abnormal cytology, Mycoplasma genitalium infection, smoking habits, younger age at sexual debut, and less frequent condom use. At baseline, women with EBV had a higher prevalence of hrHPV infection than did EBV-negative women (52% vs. 24%; HIV-adjusted PR [95% confidence interval], 1.8 [1.3-2.6]). Epstein-Barr virus-positive women had a higher prevalence than did EBV-negative women of high-grade precancer (15% vs. 2%) and abnormal cytology (37% vs. 15%), although HIV- and hrHPV-adjusted associations were not significant (high-grade precancer: PR, 2.0 [0.7-5.9]; abnormal cytology: PR, 1.4 [0.9-2.2]). In prospective analyses, a marginal association was observed between baseline EBV detection and delayed hrHPV clearance. CONCLUSIONS: Our data support a possible role for EBV as a high-risk marker or cofactor for HPV-mediated cervical cancer development.

Human Papillomavirus Prevalence Is Associated With Socioeconomic Gradients Within a Medically Underserved Appalachian Region.

OBJECTIVES: To assess type-specific prevalence of human papillomavirus (HPV) infection in a medically underserved Appalachian area and to determine whether gradients in poverty are associated with prevalence. METHODS: Among 398 women, a validated assay tested self-collected cervicovaginal samples for 37 HPV types. Three economic strata were created based on household income: below the federal poverty level for 1 person, between the FPLs for families of 1 to 4 persons, and above the FPL for a family of 4. RESULTS: Prevalence was 55.6%, with 33% having at least 1 high-risk infection. Prevalence was 27.8% for 9-valent HPV vaccine-preventable types and 39.2% for multiple types. Compared with FPL for a family of 4, women with federal poverty level for 1 person had 3 times greater prevalence, 2.3 times greater prevalence of high-risk types, and 2.5 times greater prevalence of multiple types. CONCLUSION: Human papillomavirus prevalence was high, with one-third of the sample having at least 1 high-risk type and those in the lowest-income category being disproportionately infected.

Histological Evidence of Chronic Mycoplasma genitalium-Induced Cervicitis in HIV-Infected Women: A Retrospective Cohort Study.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in inflammatory syndromes of the female reproductive tract. The objective of this study was to investigate human immunodeficiency virus (HIV)-infected women for an association between M. genitalium and cervicitis, a putative mechanism for enhanced HIV transmission efficiency to an uninfected partner. METHODS: Using a longitudinal cohort of antiretroviral therapy-adherent New Orleans women, we retrospectively screened for M. genitalium and quantitatively characterized several markers of cervical inflammation, including secreted cytokines and cytological and histological signs of leukocyte infiltration. RESULTS: We observed a high prevalence of M. genitalium (7.4%) among HIV-infected New Orleans women. Chronic M. genitalium infection was associated with increased secretion of proinflammatory cytokines, including interleukin 1ß, interleukin 6, and interleukin 8, and marked inflammatory cervical infiltrates in the cervix with enrichment of HIV target cells. Cure of M. genitalium infection resulted in ablation of all signs of inflammation. CONCLUSIONS: These findings implicate M. genitalium as an etiologic agent of cervicitis in HIV-infected women, providing a potential mechanism for enhanced HIV transmission to an uninfected partner. Screening and treatment of M. genitalium among HIV-infected individuals may be warranted to further understand this coinfection scenario, improve cervical health, and reduce the spread of HIV.

Clinical Case Of the Month: A 35 Year Old Woman with Abdominal Pain.

A 35 year old woman with past medical history of hypertension presented to the emergency department with chief complaint of severe abdominal pain for one week. The abdominal pain was located in the epigastrium and described as "cramping" and "intermittent". The pain intensity was quantified initially as 6 out of 10 on the pain scale. As the week progressed the pain became constant and radiated to the back. The intensity of the abdominal pain increased to 10 out of 10. The patient reported some relief from her pain while lying in the prone position. Initially the pain was associated with loose stools for several days. The loose stools resolved spontaneously and then the patient began to experience nausea and vomiting. Her medications included lisinopril-hydrochlorothiazide which she had been taking for the past five months. She had no history of alcohol, tobacco or illicit drug use.

Community-Based Screening for Cervical Cancer: A Feasibility Study of Rural Appalachian Women.

OBJECTIVES: To describe women's comfort levels and perceptions about their experience self-collecting cervicovaginal swabs for human papillomavirus (HPV) testing, to determine whether nurse-guided patient navigation increases the odds of women receiving a traditional Papanicolaou (Pap) test after HPV screening, and to test the hypothesis that women testing positive for oncogenic HPV would be more likely to have a subsequent Pap test than those testing negative. METHODS: A total of 400 women were recruited from 8 rural Appalachian counties, in 2013 and 2014. After completing a survey, women were provided instructions for self-collecting a cervicovaginal swab. Specimens were tested for 13 oncogenic HPV types. Simultaneously, women were notified of their test results and offered initial navigation for Pap testing. Chart-verified Pap testing within the next 6 months served as the end point. RESULTS: Comfort levels with self-collection were high: 89.2% indicated that they would be more likely to self-collect a specimen for testing, on a regular basis, compared with Pap testing. Thirty women (7.5%) had a follow-up Pap test. Women receiving added nurse-guided navigation efforts were significantly less likely to have a subsequent test (P = 0.01). Women testing positive for oncogenic HPV were no more likely than those testing negative to have a subsequent Pap test (P = 0.27). Data were analyzed in 2014. CONCLUSIONS: Rural Appalachian women are comfortable self-collecting cervicovaginal swabs for HPV testing. Furthermore, efforts to recontact women who have received an oncogenic HPV test result and an initial navigation contact may not be useful. Finally, testing positive for oncogenic HPV may not be a motivational factor for subsequent Pap testing.

Dynamics of Serum-Neutralizing Antibody Responses in Vaccinees through Multiple Doses of the BNT162b2 Vaccine.

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and IgA antibody responses when measured at six months post-boost. RBD- and spike-specific IgG4 antibody levels were markedly elevated in three-dose but not two-dose immune sera. Although strong neutralization responses were detected in two- and three-dose vaccine sera, these rapidly decayed to pre-immune levels by four and six months, respectively. While boosters enhanced serum IgG Ab reactivity and nAb responses against variant strains, all variants tested showed resistance to two- and three-dose immune sera. Our data reflect the poor durability of vaccine-induced nAb responses which are a strong predictor of protection from symptomatic SARS-CoV-2 infection. The induction of IgG4-switched humoral responses may permit extended viral persistence via the downregulation of Fc-mediated effector functions.

Characteristics of Mpox Infections in Louisiana in the 2022 Outbreak.

The 2022 outbreak of mpox in Louisiana was limited to just >300 cases, perhaps an unexpected outcome given the state's high rates of HIV and other sexually transmitted infections (STIs). We aimed to describe the local outbreak within two health centers in the New Orleans region, partnering with the Louisiana Department of Health to offer additional statewide data. We reviewed charts of persons testing positive for mpox in New Orleans from July to November 2022 at two local health centers that together accounted for half of local cases. We abstracted data on HIV status, immune function [CD4 count, viral load (VL)], antiretroviral therapy regimen, symptoms and severity of infection, vaccination status, and whether tecovirimat was administered. We present local data relative to statewide data (July 2022-January 2023). Of 103 individuals in our network for whom charts were reviewed, 96 (93%) identified as male, 52 (50%) were Black, and 69 (67%) had HIV, including 12 (17%) with uncontrolled HIV (CD4 < 200 cells/mm3 or VL >200 copies/mL). The most common presenting symptoms were rash (n = 71, 69%), fever (n = 36, 35%), and rectal pain (n = 33, 32%). Of six (6%) patients hospitalized, four (67%) were persons with HIV (PWH). Two were hospitalized for severe mpox infection with >100 lesions at presentation; both were PWH, and one had uncontrolled infection. Across the state, 307 cases have been identified and 24 have been hospitalized. Of those hospitalized, 18 (75%) were PWH, including 9 (50%) with uncontrolled HIV. The demographic data from Louisiana, a state with high prevalence of STIs and HIV/AIDS, are consistent with prior reports describing the 2022 mpox outbreak. Our results contribute to accumulating data on the severity of infection in individuals with HIV-related immunocompromise.

Independent Effects of HIV and Antiretroviral Therapy on the Oral Microbiome Identified by Multivariate Analyses.

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched HIV- subjects) showed a significant effect on both the bacteriome and mycobiome (P < 0.024) after controlling for other clinical variables (permutational multivariate analysis of variance [PERMANOVA] of Bray-Curtis dissimilarity). Cross-sectional analyses evaluating the effects of ART (HIV+ ART+ versus HIV+ ART- subjects) revealed a significant effect on the mycobiome (P < 0.007) but not the bacteriome. In parallel longitudinal analyses, ART (before versus after the initiation of ART) had a significant effect on the bacteriome, but not the mycobiome, of HIV+ and HIV- PrEP subjects (P < 0.005 and P < 0.016, respectively). These analyses also revealed significant differences in the oral microbiome and several clinical variables between HIV- PrEP subjects (pre-PrEP) and the HIV-matched HIV- group (P < 0.001). At the species level, a small number of differences in both bacterial and fungal taxa were identified within the effects of HIV and/or ART. We conclude that the effects of HIV and ART on the oral microbiome are similar to those of the clinical variables but collectively are modest overall. IMPORTANCE The oral microbiome can be an important predictor of health and disease. For persons living with HIV (PLWH), HIV and highly active antiretroviral therapy (ART) may have a significant influence on their oral microbiome. We previously reported a significant effect of HIV with ART on both the bacteriome and mycobiome. It was unclear whether ART added to or masked further effects of HIV on the oral microbiome. Hence, it was important to evaluate the effects of HIV and ART independently. For this, multivariate cross-sectional and longitudinal oral microbiome analyses (bacteriome and mycobiome) were conducted within the cohort, including HIV+ ART+ subjects and HIV+ and HIV- (preexposure prophylaxis [PrEP]) subjects before and after the initiation of ART. While we report independent significant effects of HIV and ART on the oral microbiome, we conclude that their influence is similar to that of the clinical variables but collectively modest overall.

Current oral hygiene and recreational behavioral trends in HIV disease.

OBJECTIVE: HIV disease is evolving with more HIV+ persons experiencing a high quality of life with well-controlled viremia. We recently enrolled a large cohort of HIV+ and clinically relevant HIV- persons for oral microbiome analyses that included a questionnaire related to oral hygiene and recreational behaviors. Here, the questionnaire responses were analyzed for behavioral trends within the cohort, together with trends over time by comparison to a previous geographically centered HIV+ cohort. METHODS: Data were collected by questionnaire at baseline visits as cross-sectional assessments. Multivariable analyses were conducted for associations of HIV status as well as age, race, and sex, on oral hygiene/recreational behaviors. RESULTS: HIV+ subjects had reduced brushing frequency, but increased incidence of past cleanings and frequency of dry mouth, compared to the HIV- subjects. Within the entire cohort, positive associations were identified between age and several oral hygiene practices, and between age, race, and sex for several recreational behaviors. In comparison to the historical cohort, the contemporary HIV+ cohort participated in fewer high-risk behaviors, but with similar trends for smoking and oral hygiene practices. CONCLUSION: HIV status had little association with oral hygiene and recreational behaviors despite several differences in age, race, and sex. Behavioral trends over time support a higher quality of life in people currently living with HIV.

Effect of MMR Vaccination to Mitigate Severe Sequelae Associated With COVID-19: Challenges and Lessons Learned.

Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections. In support of this, our laboratory has reported that immunization with a live attenuated fungal strain induces a novel form of trained innate immunity which provides protection against various inducers of sepsis in mice via myeloid-derived suppressor cells. Accordingly, we initiated a randomized control clinical trial with the live attenuated Measles, Mumps, Rubella (MMR) vaccine in healthcare workers in the greater New Orleans area aimed at preventing/reducing severe lung inflammation/sepsis associated with COVID-19 (ClinicalTrials.gov Identifier: NCT04475081). Included was an outcome to evaluate the myeloid-derived suppressor cell populations in blood between those administered the MMR vaccine vs placebo. The unanticipated emergency approval of several COVID-19 vaccines in the midst of the MMR clinical trials eliminated the ability to examine effects of the MMR vaccine on COVID-19-related health status. Unfortunately, we were also unable to show any impact of the MMR vaccine on peripheral blood myeloid-derived suppressor cells due to several inherent limitations (low percentages of blood leukocytes, small sample size), that also included a collaboration with a similar trial (CROWN CORONATION; ClinicalTrials.gov Identifier: NCT04333732) in St. Louis, MO. In contrast, monitoring the COVID-19 vaccine response in trial participants revealed that high COVID-19 antibody titers occurred more often in those who received the MMR vaccine vs placebo. While the trial was largely inconclusive, lessons learned from addressing several trial-associated challenges may aid future studies that test the non-specific beneficial immune effects of live attenuated vaccines.

Effect of HIV/HAART and Other Clinical Variables on the Oral Mycobiome Using Multivariate Analyses.

The oral microbiome is considered an important factor in health and disease. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial communities in a large cohort of HIV-positive and -negative individuals. The purpose of the present study was to similarly analyze the oral mycobiome in the same cohort. To identify fungi, the internal transcribed spacer 2 (ITS2) of the fungal rRNA genes was sequenced using oral rinse samples from 149 HIV-positive and 88 HIV-negative subjects that had previously undergone bacterial amplicon sequencing. Quantitative PCR was performed for total fungal content and total bacterial content. Interestingly, samples often showed predominance of a single fungal species with four major clusters predominated by Candida albicans, Candida dubliniensis, Malassezia restricta, or Saccharomyces cerevisiae Quantitative PCR analysis showed the Candida-dominated sample clusters had significantly higher total fungal abundance than the Malassezia or Saccharomyces species. Of the 25 clinical variables evaluated for potential influences on the oral mycobiome, significant effects were associated with caries status, geographical site of sampling, sex, HIV under highly active antiretroviral therapy (HAART), and missing teeth, in rank order of statistical significance. Investigating specific interactions between fungi and bacteria in the samples often showed Candida species positively correlated with Firmicutes or Actinobacteria and negatively correlated with Fusobacteria, Proteobacteria, and Bacteroidetes Our data suggest that the oral mycobiome, while diverse, is often dominated by a limited number of species per individual; is affected by several clinical variables, including HIV positivity and HAART; and shows genera-specific associations with bacterial groups.IMPORTANCE The oral microbiome is likely a key element of homeostasis in the oral cavity. With >600 bacterial species and >160 fungal species comprising the oral microbiome, influences on its composition can have an impact on both local and systemic health. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial community in a large cohort of HIV-positive and -negative subjects. We describe here a comprehensive analysis of the oral mycobiome in the same cohort. Similar to the bacterial community, HIV under highly active antiretroviral therapy (HAART) had a significant impact on the mycobiome composition, but with less impact compared to other clinical variables. Additionally, unlike the oral bacterial microbiome, the oral mycobiome is often dominated by a single species with 4 major clusters of fungal communities. Together, these results suggest the oral mycobiome has distinct properties compared with the oral bacterial community, although both are equally impacted by HIV.

HPV 6/11, 16, 18 seroprevalence in men in two US cities.

BACKGROUND: A vaccine to prevent human papillomavirus (HPV) 6, HPV 11, HPV 16, or HPV 18 and associated diseases is licensed for females, and it may be licensed for men in the future. There are limited data on HPV 6/11, 16, and/or 18 seroprevalence in men. METHODS: A total of 490 men aged 18 to 40 years were enrolled in a study of HPV in men in Tucson, AZ, and Tampa, FL. Enrolled men completed a self-administered questionnaire, and HPV serology was performed using HPV 6/11, 16, and 18 VLP assays. RESULTS: Overall, seroprevalence to HPV 16 was 12.1%, HPV 6/11 was 9.7%, and to HPV 18 was 5.4%. Seroprevalence to HPV 6/11, 16, and/or 18 was 21% and was highest among 35 to 40 year olds (48%); prevalence in this age group was significantly higher compared to the 18 to 24 year olds (adjusted odds ratio (aOR) 6.8, 95% confidence interval (CI) 3.7, 12.8). Independent predictors of seropositivity to HPV 6/11, 16, and/or 18 were older age, greater number of female sex partners in the past 3 months, and current smoking. CONCLUSIONS: HPV vaccine-type seroprevalence was highest in 35 to 40 year old men. These data on the epidemiology of HPV seroprevalence in men are useful for discussions regarding recommendations for HPV vaccine if licensed for use in men.

Trichomonas vaginalis treatment reduces vaginal HIV-1 shedding.

BACKGROUND: Vaginal HIV-1 shedding has been associated with Trichomonas vaginalis (TV) infection and could play a role in HIV transmission. The purpose of the study was to examine if effective TV treatment reduces the presence of vaginal HIV-1 RNA. METHODS: TV+ women attending an HIV outpatient clinic in New Orleans, LA, who resolved infection (n = 58) and TV-negative controls (n = 92), matched on antiretroviral therapy (ART) were examined and interviewed at baseline, 1, and 3 months. TV status was tested by culture and the amount of cell free HIV-1 RNA in the vaginal fluids was determined by the Amplicor HIV-1 Monitor ultrasensitive assay. RESULTS: : Most women (81.3%) were black and the mean age was 37.5 (SD 8.7). At baseline, 46.0% had plasma HIV-1 RNA >/=10,000 copies/mL, 26.4% had CD4<200 cells/muL, 54.7% were taking ART, and only 26.0% had detectable HIV-1 RNA in their vaginal fluids. TV-positive women who were effectively treated for TV were less likely to shed HIV vaginally at 3-months post-treatment compared to baseline (R.R. 0.34, 95% CI: 0.12-0.92, P = 0.03), whereas there was no change for TV-negative women. CONCLUSION: This study provides additional support that reducing TV infection among HIV-positive women may have an impact on the prevention of HIV transmission. Reasons for the delayed treatment effect and the effect on cervical shedding need further investigation.

Development and validation of a HPV-32 specific PCR assay.

BACKGROUND: Human Papillomavirus-32 (HPV-32) has traditionally been associated with focal-epithelial-hyperplasia (FEH). It is also present in 58% of oral warts of HIV-positive individuals whose prevalence is increasing. Current methods for the detection of HPV-32 are labor-intensive and insensitive so the goal of this work was to develop a highly sensitive and easy to use specific polymerase chain reaction (PCR) assay. MATERIALS AND METHODS: An HPV-32 L1 specific PCR assay was developed and optimized. The sensitivity and specificity was compared to previous assays utilized for detection (PGMY and MY09/11 PCR with dot blot hybridization) using cloned HPV-32 L1, the closely related HPV-42 L1 as well as clinical samples (oral swabs and fluids from 89 HIV-positive subjects). RESULTS: The HPV-32 specific PCR assay showed improved sensitivity to 5 copies of HPV-32 as compared to the PGMY PCR, MY09/11 PCR and dot blot which had a limit of detection of approximately 3,000 copies. Using the HPV-32 dot blot hybridization assay as the gold standard, the HPV-32 specific PCR assay has a sensitivity of 95.8% and 88.9% by sample and subject, respectively, and specificity was 87.8% and 58.8% by sample and subject, respectively. The low sensitivity is due to the HPV-32 specific PCR assays ability to detect more HPV-32 positive samples and may be the new gold standard. CONCLUSION: Due to the ease, sensitivity, and specificity the HPV-32 specific PCR assay is superior to previous assays and is ideal for detection of HPV-32 in large cohorts. This assay provides an excellent tool to study the natural history of HPV-32 infection and the development of oral warts.