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  • 1.

    【2hr】A Short-Term Assessment of Nascent HIV-1 Transmission Clusters Among Newly Diagnosed Individuals Using Envelope Sequence-Based Phylogenetic Analyses

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    机译 基于信封序列的系统发育分析对新诊断个体中新生的HIV-1传播簇的短期评估
    摘要：The identification of transmission clusters (TCs) of HIV-1 using phylogenetic analyses can provide insights into viral transmission network and help improve prevention strategies. We compared the use of partial HIV-1 envelope fragment of 1,070 bp with its loop 3 (108 bp) to determine its utility in inferring HIV-1 transmission clustering. Serum samples of recently (n = 106) and chronically (n = 156) HIV-1-infected patients with status confirmed were sequenced. HIV-1 envelope nucleotide-based phylogenetic analyses were used to infer HIV-1 TCs. Those were constructed using ClusterPickerGUI_1.2.3 considering a pairwise genetic distance of ≤10% threshold. Logistic regression analyses were used to examine the relationship between the demographic factors that were likely associated with HIV-1 clustering. Ninety-eight distinct consensus envelope sequences were subjected to phylogenetic analyses. Using a partial envelope fragment sequence, 42 sequences were grouped into 15 distinct small TCs while the V3 loop reproduces 10 clusters. The agreement between the partial envelope and the V3 loop fragments was significantly moderate with a Cohen's kappa (κ) coefficient of 0.59, p < .00001. The mean age (<38.8 years) and HIV-1 B subtype are two factors identified that were significantly associated with HIV-1 transmission clustering in the cohort, odds ratio (OR) = 0.25, 95% confidence interval (CI, 0.04–0.66), p = .002 and OR: 0.17, 95% CI (0.10–0.61), p = .011, respectively. The present study confirms that a partial fragment of the HIV-1 envelope sequence is a better predictor of transmission clustering. However, the loop 3 segment may be useful in screening purposes and may be more amenable to integration in surveillance programs.
  • 2.

    【2hr】HIV-1 Transmission Patterns in Men Who Have Sex with Men: Insights from Genetic Source Attribution Analysis

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    机译 与男性发生性关系的男性中的HIV-1传播方式：遗传来源归因分析的启示
    摘要：Near 60% of new HIV infections in the United Kingdom are estimated to occur in men who have sex with men (MSM). Age-disassortative partnerships in MSM have been suggested to spread the HIV epidemics in many Western developed countries and to contribute to ethnic disparities in infection rates. Understanding these mixing patterns in transmission can help to determine which groups are at a greater risk and guide public health interventions. We analyzed combined epidemiological data and viral sequences from MSM diagnosed with HIV at the national level. We applied a phylodynamic source attribution model to infer patterns of transmission between groups of patients. From pair probabilities of transmission between 14,603 MSM patients, we found that potential transmitters of HIV subtype B were on average 8 months older than recipients. We also found a moderate overall assortativity of transmission by ethnic group and a stronger assortativity by region. Our findings suggest that there is only a modest net flow of transmissions from older to young MSM in subtype B epidemics and that young MSM, both for Black or White groups, are more likely to be infected by one another than expected in a sexual network with random mixing.
  • 3.

    【2hr】Facilitators and Barriers: Clients' Perspective on the Virginia AIDS Drug Assistance Program's Affordable Care Act Implementation

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    机译 促进者和障碍者：客户对弗吉尼亚艾滋病药物援助计划的可负担医疗法案实施的看法
    摘要：Many AIDS drug assistance programs (ADAPs) purchased Affordable Care Act (ACA) qualified health plans (QHPs) for low-income people living with HIV. To date, little has been written about this from the client perspective. The study's objective was to gain information about the experience of Virginia ADAP-funded QHP enrollment and the impact of this change. English-speaking clients who were eligible for ADAP-funded QHPs were recruited at three HIV clinics in Virginia. The goal was to enroll ≥5% of those who were eligible for ADAP-funded QHPs in two Virginia Department of Health planning districts. Participants were surveyed about demographic characteristics, and semi-structured interviews were performed. Descriptive analyses were performed for cohort characteristics. Using an open coding strategy, codebooks were generated for the interviews and themes were identified. The cohort (n = 53) met our recruitment goal. Two-thirds gained their ACA knowledge at HIV clinics from case managers and social workers. Many barriers to enrollment were identified, including internet access/literacy. Almost 9 out of 10 participants had concerns about privacy, which centered on QHP's mandated use of mail-order pharmacies. Except for medication concerns, most participants had positive perceptions of the impact of QHP enrollment on their health care. HIV clinic case managers and social workers are often the primary source of knowledge for patients about insurance options and their assistance is crucial for QHP enrollment. Our findings indicate that reducing identified barriers and addressing privacy concerns by allowing people to opt out of mail order pharmacies may encourage QHP enrollment.
  • 4.

    【2hr】HIV Research for Prevention 2018: From Research to Impact Conference Summary and Highlights

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    机译 2018年预防艾滋病毒研究：从研究到影响会议总结和重点
    摘要：The HIV Research for Prevention (HIVR4P) conference is dedicated to advancing HIV prevention research, responding to a growing consensus that effective and durable prevention will require a combination of approaches as well as unprecedented collaboration among scientists, practitioners, and community workers from different fields and geographic areas. The conference theme in 2018, “From Research to Impact,” acknowledged an increasing focus on translation of promising research findings into practical, accessible, and affordable HIV prevention options for those who need them worldwide. HIVR4P 2018 was held in Madrid, Spain, on 21–25 October, with >1,400 participants from 52 countries around the globe, representing all aspects of HIV prevention research and implementation. The program included 137 oral and 610 poster presentations. This article presents a brief summary of highlights from the conference. More detailed information, complete abstracts as well as webcasts and daily Rapporteur summaries may be found on the conference website.
  • 5.

    【2hr】The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission

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    机译 细菌性阴道病不断发展的方面：对艾滋病毒传播的影响
    摘要：Bacterial vaginosis (BV) is a common yet poorly understood vaginal condition that has become a major focus of HIV transmission and immunology research. Varied terminologies are used by clinicians and researchers to describe microbial communities that reside in the female reproductive tract (FRT), which is driven, in part, by microbial genetic and metabolic complexity, evolving diagnostic and molecular techniques, and multidisciplinary perspectives of clinicians, epidemiologists, microbiologists, and immunologists who all appreciate the scientific importance of understanding mechanisms that underlie BV. This Perspectives article aims to clarify the varied terms used to describe the cervicovaginal microbiota and its “nonoptimal” state, under the overarching term of BV. The ultimate goal is to move toward language standardization in future literature that facilitates a better understanding of the impact of BV on FRT immunology and risk of sexually transmitted infections, including HIV.
  • 6.

    【2hr】Increased Cervical CD4+CCR5+ T Cells Among Kenyan Sex Working Women Using Depot Medroxyprogesterone Acetate

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    机译 使用甲羟孕酮醋酸盐仓库的肯尼亚性工作女性中子宫颈CD4 + CCR5 + T细胞增加
    摘要：Depot medroxyprogesterone acetate (DMPA) is the most common hormonal contraceptive used by women in sub-Saharan Africa, however, it has been epidemiologically associated with HIV infections. To assess whether DMPA has an effect on the number and activation of HIV target cells, this study assessed the levels and phenotype of blood- and mucosal-derived HIV target cells among women using DMPA. Thirty-five HIV uninfected women from the Pumwani Sex Worker cohort from Nairobi, Kenya were enrolled in the study (15 using DMPA and 20 not using hormonal contraception). Blood (plasma and peripheral blood mononuclear cells) and cervicovaginal (lavage, cervical cells, and ectocervical biopsies) samples were collected. Cellular phenotype and activation status were determined by flow cytometry, cytokine levels were assessed by bead array and image analysis assessed cell number and phenotype in situ. In blood, the proportion of HIV target cells and activated T cells was lower in DMPA users versus those not using hormonal contraceptives. However, analysis of cervical mononuclear cells showed that DMPA users had elevated levels of activated T cells (CD4+CD69+) and expressed lower levels of the HIV co-receptor CCR5 on a per cell basis, while tissue samples showed that in the ectocervix, DMPA users had a higher proportion of CD4+CCR5+ T cells. This study demonstrates that DMPA users had higher levels of activated T cells and HIV target cells in the genital tract. The increased pool of mucosal HIV target cells provides new biological information about the potential impact of DMPA on HIV susceptibility.
  • 7.

    【2hr】The Changing Epidemiological Profile of HIV-1 Subtype B Epidemic in Ukraine

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    机译 乌克兰HIV-1 B型流行病的流行病学概况
    摘要：While HIV-1 subtype B has caused a large epidemic in the Western world, its transmission in Ukraine remains poorly understood. We assessed the genetic diversity of HIV-1 subtype B viruses circulating in Ukraine, characterized the transmission group structure, and estimated key evolutionary and epidemiological parameters. We analyzed 120 HIV-1 subtype B pol sequences (including 46 newly generated) sampled from patients residing in 11 regions of Ukraine between 2002 and 2017. Phylogenies were estimated using maximum likelihood and Bayesian phylogenetic methods. A Bayesian molecular clock coalescent analysis was used to estimate effective population size dynamics and date the most recent common ancestors of identified clades. A phylodynamic birth–death model was used to estimate the effective reproductive number (Re) of these clades. We identified two phylogenetically distinct predominantly Ukrainian (≥75%) clades of HIV-1 subtype B. We found no significant transmission group structure for either clade, suggesting frequent mixing among transmission groups. The estimated dates of origin of both subtype B clades were around early 1970s, similar to the introduction of HIV-1 subtype A into Ukraine. Re was estimated to be 1.42 [95% highest posterior density (HPD) 1.26–1.56] for Clade 1 and 1.69 (95% HPD 1.49–1.84) for Clade 2. Evidently, the subtype B epidemic in the country is no longer concentrated in specific geographical regions or transmission groups. The study results highlight the necessity for strengthening preventive and monitoring efforts to reduce the further spread of HIV-1 subtype B.
  • 8.

    【2hr】Boosting of Markers of Fcγ Receptor Function in Anti-HIV Antibodies During Structured Treatment Interruption

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    机译 结构性治疗中断期间抗HIV抗体中Fcγ受体功能标记的增强
    摘要：Anti-HIV envelope (Env) antibodies elicit important Fc receptor functions, including FcγRIIIa-mediated natural killer cell killing of opsonized infected targets. How these antibodies evolve during HIV infection and treatment remains poorly understood. We describe changes in anti-HIV Env IgG using longitudinal samples from seroconverter subjects treated soon after infection and later during periods of structured treatment interruption (STI). Our well-validated dimeric rsFcγR binding assays combine effects of opsonizing antibody subclasses, epitopes, and geometries to provide a measure of FcγR (Fcγ receptor)-mediated functionality. IgG1 anti-Env titers diminished rapidly during antiretroviral therapy (ART; t1/2 3.0 ± 0.8 months), while the dimeric rsFcγRIIIa activity persisted longer (t1/2 33 ± 11 months), suggesting that there is maintenance of functional antibody specificities within the diminished pool of anti-HIV Env Abs. The initial antibody response to infection in two subjects was characterized by approximately fivefold higher FcγRIIIa compared with FcγRIIa binding activity. Uncoupling of FcγRIIa and FcγRIIIa activities may be a distinct feature of the early antibody response that preferentially engages FcγRIIIa-mediated effector functions. Two to three STI cycles, even with low viremia, were sufficient to boost dimeric FcγR activity in these seroconverter subjects. We hypothesize that increased humoral immunity induced by STI is a desirable functional outcome potentially achievable by therapeutic immunization during ART. We conclude that controlled viral antigen exposure under the protection of suppressive ART may be effective in eliciting FcγR-dependent function in support of viral reactivation and kill strategies.
  • 9.

    【2hr】Hemochromatosis (HFE) Gene Variants Are Associated with Increased Mitochondrial DNA Levels During HIV-1 Infection and Antiretroviral Therapy

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    机译 血色素沉着病（HFE）基因变异与HIV-1感染和抗逆转录病毒疗法过程中线粒体DNA水平升高相关
    摘要：Some HIV-associated complications involve mitochondrial dysfunction and may be less common in individuals with iron-loading HFE (hemochromatosis gene) variants. We evaluated HFE 845A and 187G alleles in relation to mitochondrial DNA (mtDNA) levels in peripheral blood mononuclear cells from 85 individuals with HIV infection on uninterrupted antiretroviral therapy (ART) for 15 or more consecutive weeks. Carriers of HFE gene variants (N = 24) had significantly higher mtDNA levels than noncarriers (N = 61), after adjusting for age, race, sex, and type of ART [adjusted β-coefficient 297, p-value < .001 for at least one HFE variant], but mtDNA declined among all individuals on study during 48 weeks on ART. Increased cellular mtDNA content may represent a compensatory response to mitochondrial stress that is influenced by iron-loading HFE variants.
  • 10.

    【2hr】Ultrasensitive Immunoassay for Simian Immunodeficiency Virus p27CA

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    机译 猿猴免疫缺陷病毒p27CA的超灵敏免疫测定
    摘要：Although effective for suppressing viral replication, combination antiretroviral treatment (cART) does not represent definitive therapy for HIV infection due to persistence of replication-competent viral reservoirs. The advent of effective cART regimens for simian immunodeficiency virus (SIV)-infected nonhuman primates (NHP) has enabled the development of relevant models for studying viral reservoirs and intervention strategies targeting them. Viral reservoir measurements are crucial for such studies but are problematic. Quantitative polymerase chain reaction (PCR) assays overestimate the size of the replication competent viral reservoir, as not all detected viral genomes are intact. Quantitative viral outgrowth assays measure replication competence, but they suffer from limited precision and dynamic range, and require large numbers of cells. Ex vivo virus induction assays to detect cells harboring inducible virus represent an experimental middle ground, but detection of inducible viral RNA in such assays does not necessarily indicate production of virions, while detection of more immunologically relevant viral proteins, including p27CA, by conventional enzyme-linked immunosorbent assays (ELISA) lacks sensitivity. An ultrasensitive digital SIV Gag p27 assay was developed, which is 100-fold more sensitive than a conventional ELISA. In ex vivo virus induction assays, the quantification of SIV Gag p27 produced by stimulated CD4+ T cells from rhesus macaques receiving cART enabled earlier and more sensitive detection than conventional ELISA-based approaches and was highly correlated with SIV RNA, as measured by quantitative reverse transcription PCR. This ultrasensitive p27 assay provides a new tool to assess ongoing replication and reactivation of infectious virus from reservoirs in SIV-infected NHP.
  • 11.

    【2hr】Early Treatment of Primary HIV Infection Is Associated with Decreased Mortality

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    机译 艾滋病毒原发感染的早期治疗与死亡率降低相关
    摘要：The aim of this study was to understand factors associated with increased mortality in a cohort of primary HIV infection (PHI) in New South Wales (NSW) over three decades. Six hundred and two patients with PHI were enrolled from 1984 to 2009. Probabilistic data linkage was performed to NSW Registry of births deaths and marriages and Australian Bureau of Statistics mortality database. Mortality was measured by crude death rate. Pre highly active antiretroviral therapy (pre-HAART) era was defined as before January 1, 1997. A Cox proportional hazard model was used to identify factors associated with death. One hundred and thirty-eight deaths occurred during 6,223 person years (PY) follow-up. Overall crude death rate was 2.2 per 100 PY (95% confidence interval [CI], 1.9–2.6), 3.6 (95% CI, 3.1–4.3)in pre-HAART era and 0.20 (95% CI, 0.08–0.47) in post-HAART era. AIDS was the most frequent cause of death (52%, 72/138), all occurring in the pre-HAART era. Of non-AIDS deaths, the leading known cause was non-AIDS cancer 8% (11/138) followed by suicide 4% (6/138). On multivariate analysis, estimated date of infection in pre-HAART era and time to commencement of ART greater than 1 year post diagnosis were more likely to be associated with death (p < .05). Mortality in PHI has decreased significantly in the post-HAART era. Non-AIDS deaths due to malignancy and suicide are emerging as leading causes in this population in the post-HAART era. Time to starting ART greater than 1 year was associated with increased mortality.
  • 12.

    【2hr】Broad-Spectrum and Personalized Guide RNAs for CRISPR/Cas9 HIV-1 Therapeutics

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    机译 CRISPR / Cas9 HIV-1治疗药物的广谱和个性化指导RNA
    摘要：The clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 system has been used to excise the HIV-1 proviral genome from latently infected cells, potentially offering a cure for HIV-infected patients. Recent studies have shown that most published HIV-1 guide RNAs (gRNAs) do not account for the diverse viral quasispecies within or among patients, which continue to diversify with time even in long-term antiretroviral therapy (ART)-suppressed patients. Given this observation, proviral genomes were deep sequenced from 23 HIV-1-infected patients in the Drexel Medicine CNS AIDS Research and Eradication Study cohort at two different visits. Based on the spectrum of integrated proviral DNA polymorphisms observed, three gRNA design strategies were explored: based on the patient's own HIV-1 sequences (personalized), based on consensus sequences from a large sample of patients [broad-spectrum (BS)], or a combination of both approaches. Using a bioinformatic algorithm, the personalized gRNA design was predicted to cut 46 of 48 patient samples at 90% efficiency, whereas the top 4 BS gRNAs (BS4) were predicted to excise provirus from 44 of 48 patient samples with 90% efficiency. Using a mixed design with the top three BS gRNAs plus one personalized gRNA (BS3 + PS1) resulted in predicted excision of provirus from 45 of 48 patient samples with 90% efficiency. In summary, these studies used an algorithmic design strategy to identify potential BS gRNAs to target a spectrum of HIV-1 long teriminal repeat (LTR) quasispecies for use with a small HIV-1-infected population. This approach should advance CRISPR/Cas9 excision technology taking into account the extensive molecular heterogeneity of HIV-1 that persists in situ after prolonged ART.
  • 13.

    【2hr】Differentiation of Type 1 and Type 2 Myocardial Infarctions Among HIV-Infected Patients Requires Adjudication Due to Overlap in Risk Factors

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    机译 HIV感染患者中1型和2型心肌梗塞的鉴别需要危险因素重叠的裁决
    摘要：The Universal Myocardial infarction (MI) definition divides MIs into different types. Type 1 MIs (T1MI) result spontaneously from atherosclerotic plaque instability. Type 2 MIs (T2MI) are due to secondary causes of myocardial oxygen demand/supply mismatch such as occurs with sepsis. T2MI are much more common among those with HIV than in the general population. T1MI and T2MI have different mechanisms, risk factors, and potential treatments suggesting that they should be distinguished to achieve a better scientific understanding of MIs in HIV. We sought to determine whether MI type could be accurately predicted by patient characteristics without adjudication in HIV-infected individuals. We developed a statistical model to predict T2MI versus T1MI using adjudicated events from six sites utilizing demographic characteristics, traditional cardiovascular, and HIV-related risk factors. Validation was assessed in a seventh site via mean calibration, and discrimination level was assessed by the area under the curve (AUC). Of 812 MIs, 388 were T2MI. HIV-related factors including hepatitis C infection were predictive of T2MI, whereas traditional cardiovascular risk factors including total cholesterol predicted T1MI. The score predicted 69 T2MI in the validation sample resulting in poor calibration, given that 90 T2MIs were observed. The development sample AUC was 0.75 versus 0.65 in the validation sample, suggesting relatively poor discrimination. The level of discrimination to predict MI type based on patient characteristics is insufficient for individual level prediction. Adjudication is required to distinguish MI types, which is necessary to advance understanding of this important outcome among HIV populations.
  • 14.

    【2hr】A Summary of the Third Annual HIV Microbiome Workshop

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    机译 第三届年度艾滋病毒微生物学研讨会总结
    摘要：Our microbial cotravelers have increasingly apparent roles in both maintaining health and causing disease in several organ systems. Investigators gather annually at the National Institutes of Health to present new discoveries regarding the role of the microbiome in human health and a special focus on persons living with HIV. Here, we summarize the discussions from the third annual Virology Education workshop on the microbiome in HIV, which took place in October of 2017.
  • 15.

    【2hr】HIV-1 Transmission Clustering and Phylodynamics Highlight the Important Role of Young Men Who Have Sex with Men

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    机译 HIV-1传播聚类和系统动力学突出了与男性发生性关系的年轻男子的重要作用
    摘要：More persons living with HIV reside in the Southern United States than in any other region, yet little is known about HIV molecular epidemiology in the South. We used cluster and phylodynamic analyses to evaluate HIV transmission patterns in middle Tennessee. We performed cross-sectional analyses of HIV-1 pol sequences and clinical data collected from 2001 to 2015 among persons attending the Vanderbilt Comprehensive Care Clinic. Transmission clusters were identified using maximum likelihood phylogenetics and patristic distance differences. Demographic, risk behavior, and clinical factors were assessed evaluating “active” clusters (clusters including sequences sampled 2011–2015) and associations estimated with logistic regression. Transmission risk ratios for men who have sex with men (MSM) were estimated with phylodynamic models. Among 2915 persons (96% subtype-B sequences), 963 (33%) were members of 292 clusters (distance ≤1.5%, size range 2–39). Most clusters (62%, n = 690 persons) were active, either being newly identified (n = 80) or showing expansion on existing clusters (n = 101). Correlates of active clustering among persons with sequences collected during 2011–2015 included MSM risk and ≤30 years of age. Active clusters were significantly more concentrated in MSM and younger persons than historical clusters. Young MSM (YMSM) (≤26.4 years) had high estimated transmission risk [risk ratio = 4.04 (2.85–5.65) relative to older MSM] and were much more likely to transmit to YMSM. In this Tennessee cohort, transmission clusters over time were more concentrated by MSM and younger age, with high transmission risk among and between YMSM, highlighting the importance of interventions among this group. Detecting active clusters could help direct interventions to disrupt ongoing transmission chains.
  • 16.

    【2hr】Characterization of the Transmitted Virus in an Ongoing HIV-1 Epidemic Driven by Injecting Drug Use

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    机译 在注射毒品驱动的持续性HIV-1流行病中传播病毒的特征
    摘要：Understanding features of the HIV-1 transmission process has the potential to inform biological interventions for prevention. We have examined the transmitted virus in a cohort of people who inject drugs and who are at risk of HIV-1 infection through blood contamination when injecting in a group. This study focused on seven newly infected participants in St. Petersburg, Russia, who were in acute or early infection. We used end-point dilution polymerase chain reaction to amplify single viral genomes to assess the complexity of the transmitted virus. We also used deep sequencing to further assess the complexity of the virus. We interpret the results as indicating that a single viral variant was transmitted in each case, consistent with a model where the exposure to virus during transmission was limited. We also looked at phenotypic properties of the viral Env protein in isolates from acute and chronic infection. Although differences were noted, there was no consistent pattern that distinguished the transmitted variants. Similarly, despite the reduced genetic heterogeneity of the more recent subtype A HIV-1 epidemic in St. Petersburg, we did not see reduced variance in the neutralization properties compared to isolates from the more mature subtype C HIV-1 epidemic. Finally, in looking at members of injecting groups related to the acute HIV-1 infection/early subjects, we found examples of sequence linkage consistent with ongoing and rapid spread of HIV-1 in these groups. These studies emphasize the dynamic nature of this epidemic and reinforce the idea that improved prevention methods are needed.
  • 17.

    【2hr】Comparative Assessment of Small and Large Intestine Biopsies for Ex Vivo HIV-1 Pathogenesis Studies

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    机译 体外HIV-1发病机制研究的小肠和大肠活检的比较评估
    摘要：Ex vivo mucosal explants have become a mainstay of HIV-1 studies using human tissue. In this study, we examine the baseline phenotypic and virologic differences between biopsies derived from the small intestine (SI) and large intestine (LI) for use in ex vivo explant studies. To do this, we collected endoscopic mucosal biopsies from both SI and LI from the same healthy, HIV-seronegative participants. Mucosal mononuclear cell phenotypes and quantity were compared using flow cytometry. Comparative HIV-1 infectibility of the explants was assessed using an ex vivo explant HIV-1 infection assay. We found that all biopsies had similar numbers of T cells per biopsy. While the percentage of CD4+ T cells from SI biopsies expressed significantly more activation markers (CD38, HLA-DR) and HIV coreceptors (CXCR4, CCR5), the absolute numbers of activated CD4+ T cells were similar between both sites. LI explants, however, supported more efficient HIV-1 infection, as evidenced by earlier rise in p24 accumulation and greater percent of infected explants at limiting infectious doses. These results suggest that explants from LI biopsies support more efficient HIV-1 infection than SI biopsies, despite similar numbers of available, activated HIV-1 target cells. These findings highlight important differences in LI and SI explants, which must be considered in designing and interpreting ex vivo HIV-1 infection studies, and suggest that factors within the tissue other than target cell number and activation state may play a role in regulating HIV-1 infection.
  • 18.

    【2hr】A Longitudinal Assessment of Cervical Inflammation and Immunity Associated with HIV-1 Infection, Hormonal Contraception, and Pregnancy

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    机译 与HIV-1感染，激素避孕和妊娠相关的宫颈炎症和免疫的纵向评估
    摘要：Hormonal contraception (HC), particularly injectable depot-medroxyprogesterone acetate (DMPA), has been associated with increased HIV acquisition and higher levels of cervical regulated upon activation, normal T-cell expressed, and secreted (RANTES), also associated with HIV seroconversion. Longitudinal changes in cervical immunity associated with DMPA and combined oral contraceptives (COCs) have not been studied. Cervical samples from 216 HIV seroconverters in Uganda and Zimbabwe with matched samples from 727 HIV-uninfected controls were collected at two quarterly visits before (t − 2, t − 1), at (t0), and two visits following (t + 1, t + 2) HIV seroconversion and corresponding visits for HIV-negative controls. We measured 10 biomarkers of inflammation and immunity and used generalized linear models to estimate and compare biomarker levels across HIV status, contraceptive, and pregnancy groups. Biomarkers remained relatively stable across visits for controls, while in HIV-infected women cervical immunity started to change before seroconversion with RANTES and BD-2 increased and secretory leukocyte protease inhibitor (SLPI) decreased at t − 1 and continued to change at t0 with ICAM-1 up and IL-8 down and with more biomarkers after seroconversion (IL-1β, IL-6, MIP-3α, VEGF, and IL-1RA down and IL-1RA:IL-1β ratio up). In multivariable analyses, seroconverters had higher BD-2 at t − 1, higher RANTES and lower SLPI from t − 1 through t + 2, and lower IL-8 and IL-1RA at and/or after seroconversion compared to nonseroconverters. Compared to non-HC users, DMPA users had higher RANTES at all visits and lower BD-2 at t − 2 through t0, while COC users and pregnant women had higher IL-8 and SLPI at all visits; COC users also had lower BD-2 preseroconversion; pregnant women had lower RANTES at t0 − t + 2. Longitudinal patterns of cervical immunity differ between HIV seroconverters and HIV-negative women; seroconverters demonstrate increased RANTES and decreased SLPI starting before and continuing postseroconversion. Furthermore, these patterns are differentially regulated by DMPA, COC, and pregnancy.
  • 19.

    【2hr】Early Life HIV-1 Immunization: Providing a Window for Protection Before Sexual Debut

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    机译 早期的HIV-1免疫：为性首次亮相提供保护的窗口
    摘要：Limited success of current HIV-1 vaccines warrants new approaches. We discuss feasibility and potential benefits of early life HIV-1 immunization followed by vaccine boosts during childhood that may enable maturation of vaccine-induced broad anti-HIV-1 immunity over several years. By initiating this immunization approach in the very young, well before sexual debut, such a strategy may dramatically reduce the risk of HIV-1 infection.
  • 20.

    【2hr】Qualitative Consumer Research on Acceptance of Long-Acting Pre-Exposure Prophylaxis Products Among Men Having Sex with Men and Medical Practitioners in the United States

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    机译 在美国，与男男性接触者和医疗从业人员接受长效暴露前预防产品的定性消费者研究
    摘要：Pre-exposure prophylaxis (PrEP) with oral Truvada® prevents HIV infection. However, the adherence to pill taking required for efficacy has sparked interest in developing new antiretroviral delivery systems that decrease such demands. Long-acting formulations, such as injections and implants, represent promising options that require less frequent adherence. It is important, however, that development of these new modalities be driven by understanding of the value seen in them by target users to maximize their uptake. To identify the key product features that impact user acceptance, we used a three-phase marketing research approach. In this study, we describe the results of the first-phase, qualitative focus group research performed in Chicago and San Francisco that explored subjective perceptions of oral versus alternative PrEP modalities among men having sex with men (MSM) and medical practitioners caring for MSM. Data revealed that potential value in long-acting PrEP lies more in simplifying the lives of users rather than in making them more confident in their adherence. The results provide an important guidance for designing and promoting these future long-acting products to enhance their contribution to increasing the current limited uptake of PrEP that will better stem the HIV epidemic.
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