Macrophage-Derived Factors with the Potential to Contribute to Pathogenicity of HIV-1 and HIV-2: Role of CCL-2/MCP-1.

Human immunodeficiency virus type 2 (HIV-2) is known to be less pathogenic than HIV-1. However, the mechanism(s) underlying the decreased HIV-2 pathogenicity is not fully understood. Herein, we report that ß-chemokine CCL2 expression was increased in HIV-1-infected human monocyte-derived macrophages (MDM) but decreased in HIV-2-infected MDM when compared to uninfected MDM. Inhibition of CCL2 expression following HIV-2 infection occurred at both protein and mRNA levels. By microarray analysis, quantitative PCR, and Western blotting, we identified that Signal Transducer and Activator of Transcription 1 (STAT1), a critical transcription factor for inducing CCL2 gene expression, was also reduced in HIV-2-infected MDM. Blockade of STAT1 in HIV-infected MDM using a STAT1 inhibitor significantly reduced the production of CCL2. In contrast, transduction of STAT1-expressing pseudo-retrovirus restored CCL2 production in HIV-2-infected MDM. These findings support the concept that CCL2 inhibition in HIV-2-infected MDM is meditated by reduction of STAT1. Furthermore, we showed that STAT1 reduction in HIV-2-infected MDM was regulated by the CUL2/RBX1 ubiquitin E3 ligase complex-dependent proteasome pathway. Knockdown of CUL2 or RBX1 restored the expression of STAT1 and CCL2 in HIV-2-infected MDM. Taken together, our findings suggest that differential regulation of the STAT1-CCL2 axis may be one of the mechanisms underlying the different pathogenicity observed for HIV-1 and HIV-2.

Advancing Digital Health Innovation in Oncology: Priorities for High-Value Digital Transformation in Cancer Care.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives.

Oncology Medical Home: ASCO and COA Standards.

PURPOSE: To provide Standards on the basis of evidence and expert consensus for a pilot of the Oncology Medical Home (OMH) certification program. The OMH model is a system of care delivery that features coordinated, efficient, accessible, and evidence-based care and includes a process for measurement of outcomes to facilitate continuous quality improvement. The OMH pilot is intended to inform further refinement of Standards for OMH model implementation. METHODS: An Expert Panel was formed, and a systematic review of the literature on the topics of OMH, clinical pathways, and survivorship care plans was performed using PubMed and Google Scholar. Using this evidence base and an informal consensus process, the Expert Panel developed a set of OMH Standards. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: Three comparative peer-reviewed studies of OMH met the inclusion criteria. In addition, the results from 16 studies of clinical pathways and one systematic review of survivorship care plans informed the evidence review. Limitations of the evidence base included the small number of studies of OMH and lack of longer-term outcomes data. More data were available to inform the specific Standards for pathways and survivorship care; however, outcomes were mixed for the latter intervention. The Expert Panel concluded that in the future, practices should be encouraged to publish the results of OMH interventions in peer-reviewed journals to improve the evidence base. STANDARDS: Standards are provided for OMH in the areas of patient engagement, availability and access to care, evidence-based medicine, equitable and comprehensive team-based care, quality improvement, goals of care, palliative and end-of-life care discussions, and chemotherapy safety. Additional information, including a Standards implementation manual, is available at www.asco.org/standards.

Integrating Somatic and Germline Next-Generation Sequencing Into Routine Clinical Oncology Practice.

Next-generation sequencing (NGS) is rapidly expanding into routine oncology practice. Genetic variations in both the cancer and inherited genomes are informative for hereditary cancer risk, prognosis, and treatment strategies. Herein, we focus on the clinical perspective of integrating NGS results into patient care to assist with therapeutic decision making. Five key considerations are addressed for operationalization of NGS testing and application of results to patient care as follows: (1) NGS test ordering and workflow design; (2) result reporting, curation, and storage; (3) clinical consultation services that provide test interpretations and identify opportunities for molecularly guided therapy; (4) presentation of genetic information within the electronic health record; and (5) education of providers and patients. Several of these key considerations center on informatics tools that support NGS test ordering and referencing back to the results for therapeutic purposes. Clinical decision support tools embedded within the electronic health record can assist with NGS test utilization and identifying opportunities for targeted therapy including clinical trial eligibility. Challenges for project and change management in operationalizing NGS-supported, evidence-based patient care in the context of current information technology systems with appropriate clinical data standards are discussed, and solutions for overcoming barriers are provided.

Transitioning Clinical Practice Guidelines into the Electronic Health Record through Clinical Pathways.

Clinical practice guidelines in oncology provide an evidence-based roadmap for most cancer care delivery but often lack directions for specific patient factors and disease conditions. Clinical pathways serve as a real-time clinical decision support system to translate guidelines to clinical practice. Pathways allow for the creation of a standardized, multidimensional roadmap for the continuum of care that can support clinical decision-making, maintain optimal outcomes, and limit unnecessary variation in cancer care. Here we describe the process to develop and implement clinical pathways in the electronic health record. This process includes building the appropriate foundation for a clinical pathways team with supports in the institutional ecosystem, creating visual representations of care paths, formalizing the pathway approval process, and translating clinical pathways into an electronic health record-integrated clinical decision support tool.

Time Since First Acting on Same-Sex Attraction and Recreational Drug Use among Men Who Have Sex With Men (MSM): Is There an Effect of "Gay Age"?

BACKGROUND: Men who have sex with men (MSM) have higher rates of substance use compared to men who have sex with women. Among MSM, drug use is linked to higher-risk sexual behavior and acquisition of HIV and other sexually transmitted infections. OBJECTIVES: We hypothesize that time since first acting on one's same sex attraction, or one's "gay age", could be predictive of drug using behavior. METHODS: We examined this question among 176 MSM, aged 18-35, presenting at a public sexual health clinic. Behavioral data were captured using interviewer- and self-administered surveys and clinical data were extracted from medical records. We used modified Poisson regression to examine associations between gay age and recent recreational drug use, and separately, between gay age and recent marijuana use. RESULTS: In total, 43% of participants reported recent marijuana use and 26% of participants reported recent use of other drugs. The associations between gay age and marijuana use and other drug use varied by HIV status. After adjustment for biological age, race, and education, a one-year increase in gay age was associated with significantly increased drug use among HIV-negative men (adjusted prevalence ratio (aPR): 1.08; 95% confidence interval (CI): 1.03-1.14), but we observed no association between gay age and drug use among HIV-positive men (aPR: 0.96, 95% CI: 0.86-1.07). Gay age was not associated with marijuana use in HIV-negative (aPR: 1.00, 95% CI: 0.95-1.04) or HIV-positive (aPR: 1.06, 95% CI: 0.98-1.14) men. CONCLUSIONS: In summary, HIV-negative MSM who had experienced more time since first same-sex experience had significantly increased prevalence of recent drug use.

Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015.

Background: Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae. Methods: In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015. Results: Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52). Conclusions: Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission.

Lubricant Use and Rectal Chlamydial and Gonococcal Infections Among Men Who Engage in Receptive Anal Intercourse.

BACKGROUND: Use of lubricants during anal intercourse is very common among men who have sex with men. However, few studies have evaluated associations between specific lubricants and rectal sexually transmitted infections (STIs). METHODS: Between July 2012 and October 2013, we conducted a cross-sectional study of men who have sex with men recruited from an urban, public sexual health clinic. In a self-administered survey, participants identified the lubricants used and frequency of lubricant use in the previous three months. Among men reporting any receptive anal intercourse (RAI) in the previous 3 months, we used multivariable binomial regression models to analyze associations between recent use of 9 specific lubricants and prevalent rectal chlamydia, rectal gonorrhea, and either rectal infection. RESULTS: Twenty-five percent of the 146 participants had rectal chlamydial infection and 21% had rectal gonococcal infection; 37% had either (chlamydial or gonococcal) infection. Three-quarters reported always or almost always using lubricant during recent receptive anal intercourse. After adjustment for age, race, human immunodeficiency virus status, and condom use, Gun Oil (adjusted prevalence ratio [aPR], 1.99; 95% confidence interval [CI], 1.04-3.80) and Slick (aPR, 3.55; 95% CI, 1.38-9.12) were significantly associated with prevalent gonococcal infection. No lubricants were significantly associated with prevalent rectal chlamydia, but in analyses of either rectal infection, precum (aPR, 1.68; 95% CI, 1.06-2.66), Vaseline (aPR, 1.70; 95% CI, 1.10-2.64), and baby oil (aPR, 2.26; 95% CI, 1.43-3.57) were all significantly associated with prevalent rectal infection. CONCLUSIONS: Several lubricants were significantly associated with increased prevalence of rectal STI. Longitudinal studies are needed to examine any causal relationship between specific lubricants and STI acquisition.

Recent Biomarker-Confirmed Unprotected Vaginal Sex, But Not Self-reported Unprotected Sex, Is Associated With Recurrent Bacterial Vaginosis.

BACKGROUND: Self-reported unprotected vaginal sex seems to increase risk of bacterial vaginosis (BV). However, the validity of self-reports is questionable, given their inconsistency with more objective measures of recent semen exposure such as detection of prostate-specific antigen (PSA). We examined whether recent unprotected sex, as measured both by PSA detection on vaginal swabs and by self-report, was associated with increased BV recurrence. METHODS: We analyzed randomized trial data from nonpregnant, BV-positive adult women recruited from a sexually transmitted disease clinic. Participants received BV therapy at enrollment and were scheduled to return after 4, 12, and 24 weeks. Bacterial vaginosis (by Nugent score) and PSA were measured at each visit. We used Cox proportional hazards models to examine the association between PSA positivity and recurrent BV. We also evaluated associations between self-reported unprotected sex (ever/never since the last visit and in the last 48 hours, analyzed separately) and recurrent BV. RESULTS: Prostate-specific antigen and BV results were available for 96 women who contributed 226 follow-up visits. Prostate-specific antigen positivity was associated with increased BV recurrence (adjusted hazard ratio [aHR], 2.32; 95% confidence interval [CI], 1.28-4.21). In contrast, we observed no significant increase in BV recurrence among women self-reporting unprotected sex since the last visit (aHR, 1.63; 95% CI, 0.77-3.43) or in the last 48 hours (aHR, 1.28; 95% CI, 0.70-2.36). CONCLUSIONS: Estimates from earlier studies linking self-reported unprotected sex and BV may be biased by misclassification. Biomarkers can improve measurement of unprotected sex, a critical exposure variable in sexual health research.

Beyond Anal Sex: Sexual Practices of Men Who have Sex with Men and Associations with HIV and Other Sexually Transmitted Infections.

INTRODUCTION: Unprotected anal intercourse is often used as a single indicator of risky behavior in men who have sex with men (MSM), yet MSM engage in a variety of behaviors that have unknown associations with sexually transmitted infection (STI) and HIV. AIM: To assess the prevalence of a wide range of sexual behaviors and their associations with prevalent STI and HIV. METHODS: We used a standardized, self-administered survey to collect behavioral data for this cross-sectional study of 235 MSM seeking care in a public clinic for sexually transmitted diseases. MEAN OUTCOME MEASURES: Using modified Poisson regression, we generated unadjusted and adjusted prevalence ratios (PRs) to characterize associations between recent participation in each behavior and prevalent STI and HIV. RESULTS: Participants' median age was 26 years. One third (35%) were positive for STI. STI prevalence was significantly associated with using sex slings (adjusted PR [aPR] = 2.35), felching (aPR = 2.22), group sex (aPR = 1.86), fisting (aPR = 1.78), anonymous sex (aPR = 1.51), and sex toys (aPR = 1.46). HIV prevalence was 17% and was significantly associated with fisting (aPR = 4.75), felching (aPR = 4.22), enemas (aPR = 3.65), and group sex (aPR = 1.92). CONCLUSION: Multiple behaviors were significantly associated with prevalent STI and HIV in adjusted analyses. To provide a more comprehensive understanding of sexual risk in MSM, prospective studies are needed to examine whether these behaviors are causally associated with HIV and STI acquisition.

Group Sex and Prevalent Sexually Transmitted Infections Among Men Who Have Sex with Men.

We evaluated the direct relation between group sex and prevalent sexually transmitted infections (STI) in a cross-sectional study of men who have sex with men (MSM) presenting at an urban STI clinic in the Midwestern US. Among 231 men who enrolled and reported that they have sex with men, we collected behavioral data using a combination of interviewer and self-administered surveys and extracted STI data from electronic health records. We used modified Poisson regression to examine the unadjusted and adjusted associations between group sex participation and prevalent STI. One-quarter of participants (n = 58) reported group sex participation in the last 3 months. Eighteen percent of participants (n = 42) had gonorrhea and 19 % (n = 45) had chlamydial infection. Men who reported recent group sex were more likely to be HIV-positive, to report recent drug use, and to report unprotected receptive anal intercourse in the past 3 months. After adjustment for age, race, and recent drug use, recent participation in group sex was associated with prevalent gonorrhea infection (prevalence ratio [PR] = 2.11, 95 % confidence interval [CI] = [1.13, 3.95]) but not chlamydia infection (PR = 1.03, 95 % CI = [0.58, 1.84]). We performed a sensitivity analysis in which we also adjusted for unprotected receptive anal intercourse and the results were not substantively changed. In summary, participation in group sex in the past 3 months was associated with a more than twofold increased prevalence of gonorrhea, but not with chlamydia. These findings support group sex participation as a potential contributor to increased STI prevalence.

Body image and sexually transmissible infection prevalence among men who have sex with men.

Compared with men who have sex with women, some evidence suggests that men who have sex with men (MSM) have increased prevalence of body image dissatisfaction. MSM also have a higher prevalence of sexually transmissible infections (STIs) than other population groups. As part of a cross-sectional study, body image among 104 MSM using the standardised, validated Male Body Attitudes Scale was assessed. Associations between body image and prevalent STI were examined. Body image was not associated with prevalent STI in unadjusted [prevalence ratio (PR): 1.14, 95% confidence interval (CI): 0.86-1.52] or adjusted analyses (PR: 1.17, 95% CI: 0.89-1.53).

High prevalence of rectal gonorrhea and Chlamydia infection in women attending a sexually transmitted disease clinic.

BACKGROUND: Testing women for urogenital Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) is common in sexually transmitted disease (STD) clinics. However, women may not be routinely tested for rectal GC/CT. This may lead to missed infections in women reporting anal intercourse (AI). METHODS: This was a retrospective review of all women who underwent rectal GC/CT testing from August 2012 to June 2013 at an STD clinic in Columbus, Ohio. All women who reported AI in the last year had a rectal swab collected for GC/CT nucleic acid amplification testing (n=331). Using log-binomial regression models, we computed unadjusted and adjusted associations for demographic and behavioral factors associated with rectal GC/CT infection. RESULTS: Participants (n=331) were 47% African-American, with median age of 29 years. Prevalence of rectal GC was 6%, rectal CT was 13%, and either rectal infection was 19%. Prevalence of urogenital GC and CT was 7% and 13% respectively. Among women with rectal GC, 14% tested negative for urogenital GC. Similarly, 14% of women with rectal CT tested negative for urogenital CT. In unadjusted analyses, there was increased rectal GC prevalence among women reporting sex in the last year with an injection drug user, with a person exchanging sex for drugs or money, with anonymous partners, and while intoxicated/high on alcohol or illicit drugs. After multivariable adjustment, no significant associations persisted, but a trend of increased rectal GC prevalence was observed for women <26 years of age (p=0.06) and those reporting sex while intoxicated/high on alcohol or drugs (p=0.05). For rectal CT, only age <26 years was associated with prevalent infection in unadjusted models; this association strengthened after multivariable adjustment (prevalence ratio: 6.03; 95% confidence interval: 2.29-15.90). CONCLUSION: Nearly one in five women who reported AI in the last year had rectal GC or CT infection. Urogenital testing alone would have missed 14% of rectal infections. Standardized guidelines would increase rectal GC/CT testing in women and help detect missed infections.

A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis.

OBJECTIVE: Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. STUDY DESIGN: This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban sexually transmitted disease clinic (clinicaltrials.gov registration NCT01450462). All participants received 500 mg of oral metronidazole twice daily for 7 days. Intervention participants (n = 59) also received 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks; control women (n = 59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12, and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. RESULTS: Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. CONCLUSION: Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not associated with decreased BV recurrence in this high-risk sexually transmitted disease clinic population.

Prostate-specific antigen is unlikely to be a suitable biomarker of semen exposure from recent unprotected receptive anal intercourse in men who have sex with men.

A biomarker of unprotected receptive anal intercourse could improve validity of sexual behavior measurement. We quantified prostate-specific antigen (PSA) from rectal swabs from men who have sex with men (MSM). One swab was PSA positive. Using current methods, PSA is an inadequate biomarker of recent unprotected receptive anal intercourse in men who have sex with men.

HIV, rectal chlamydia, and rectal gonorrhea in men who have sex with men attending a sexually transmitted disease clinic in a midwestern US city.

BACKGROUND: Men who have sex with men (MSM) who report receptive anal intercourse (RAI) are currently recommended to undergo at least annual screening for rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection. METHODS: Using standard culture methods, we assessed the prevalence of rectal GC/CT among MSM who reported RAI in the last year (n = 326) at an urban sexually transmitted disease (STD) clinic in a midwestern US city. A subset (n = 125) also underwent rectal GC/CT screening via nucleic acid amplification testing. We examined the associations between HIV status and prevalence of rectal GC and rectal CT using unadjusted and adjusted logistic regression models. RESULTS: The prevalence of rectal GC, rectal CT, and either rectal infection was 9%, 9%, and 15% by culture and 24%, 23%, and 38% by nucleic acid amplification testing, respectively. HIV was not associated with rectal GC prevalence in unadjusted or adjusted analyses. HIV-positive status was significantly associated with increased rectal CT prevalence in unadjusted models (odds ratio, 2.18; 95% confidence interval, 1.04-4.60); this association increased after multivariable adjustment (odds ratio, 3.14; 95% confidence interval, 1.37-7.19). CONCLUSIONS: Men who have sex with men reporting RAI had a high prevalence of rectal GC and rectal CT. HIV-positive status was significantly associated with prevalent rectal CT but not with prevalent rectal GC.

Phase I Study of Topotecan, Ifosfamide, and Etoposide (TIME) with autologous stem cell transplant in refractory cancer: pharmacokinetic and pharmacodynamic correlates.

PURPOSE: To determine the maximum tolerated dose (MTD) of topotecan in combination with ifosfamide, mesna, and etoposide (TIME), followed by autologous hematopoietic cell transplant (HCT), in patients with chemotherapy-refractory malignancies. EXPERIMENTAL DESIGN: Patients were treated with (in mg/m(2)/d) ifosfamide 3,333, mesna 3,333, and topotecan 3.3 to 28.3 during days -8 through -6 and etoposide 500 (days -5 through -3) followed by HCT on day 0. Once MTD was defined, we expanded this dosing cohort to include patients with high-risk lymphoma due to activity seen during dose escalation. Topotecan pharmacokinetic analyses were carried out, and topoisomerase I levels and activity were measured. RESULTS: The topotecan MTD in this regimen was 64 mg/m(2) (21.3 mg/m(2)/d). Mucositis was dose limiting and correlated with topotecan dose level and area under the curve (AUC). Dose level was also correlated with length of hospitalization, number of days of parenteral nutrition, and neutrophil and platelet engraftment. Topotecan AUC was significantly correlated with time to platelet recovery. The baseline peripheral blood mononuclear cell topoisomerase I level was found to be a significant positive predictor for overall and progression-free survival. Topotecan AUC was positively correlated with dose level, with a trend toward decreasing clearance with increasing dose. CONCLUSION: Topotecan can be a useful drug in the high-dose setting given its activity in some malignancies when given in standard dose. Pharmacokinetic monitoring may be a valuable tool for optimizing the use of topotecan and to avoid toxicity seen with high-systemic exposures. Baseline topoisomerase I levels may have an important role in predicting topotecan efficacy.

Prevalence of gonococcal and chlamydial infection in 2009 in 2 populations in a midwestern city.

The purpose of this cross-sectional study was to assess the 2009 prevalence of chlamydial and gonococcal infection in 2 populations in a midwestern city in the United States: patients at a public sexually transmitted disease (STD) clinic, and individuals seeking human immunodeficiency virus (HIV) counseling and testing services at an AIDS community organization. We characterized STD prevalence in a random sample of 592 STD clinic patients and a convenience sample of 471 individuals agreeing to STD testing through outreach efforts at the community organization. The STD clinic population was 59% male, 60% black, with 3.1 mean sex partners in the last year. The community organization population was 72% male, 19% black, with a mean of 4.3 partners in the last year. The prevalence of both chlamydial and gonococcal infections was consistently higher in STD clinic patients than at the community organization (18% vs 4%). Prevalence of chlamydial infection was higher than prevalence of gonococcal infection in both populations (chlamydial infection, 3% and 13% at the STD clinic and community organization, respectively; vs gonococcal infection, 1% and 7%, respectively). Factors significantly associated with increased odds of gonococcal/chlamydial infection at the STD clinic include unmarried status, younger age, at least 6 partners in the last year, and unprotected sex in the last year. At the community organization, the only factor significantly associated with increased odds of gonococcal/chlamydial infection was lower educational attainment. Our findings confirm that STD prevalence differs widely by population group. Given these differences, local approaches to STD control should also be carefully targeted to specific subgroups.

Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication.

Platelet factor 4 (CXCL4), a member of the CXC chemokine subfamily released in high amounts by activated platelets, has been identified as a monocyte survival factor that induces monocyte differentiation into macrophages. Although CXCL4 has been shown to have biological effects unique to chemokines, nothing is known about the role of CXCL4-derived human macrophages or CXCL4 in human immunodeficiency virus (HIV) disease. In this study, CXCL4-derived macrophages are compared with macrophage-colony stimulating factor (M-CSF)-derived macrophages for their ability to support HIV-1 replication. We show that CXCL4-derived macrophages can be infected with macrophage-tropic HIV-1 that uses either CC-chemokine receptor 5 (CCR5) or CXC-chemokine receptor 4 (CXCR4) as a co-receptor for viral entry. We also find that M-CSF and the chemokines, monocyte chemoattractant protein 1 (MCP-1; CCL2) and macrophage-inflammatory-protein-1-alpha (MIP-1alpha; CCL3) are produced upon R5- and X4-tropic HIV-1 replication in both M-CSF- and CXCL4-derived human macrophages. In addition, CXCL4 added to M-CSF-derived macrophages after virus adsorption and maintained throughout the infection enhances HIV-1 replication. We thus propose a novel role for CXCL4 in HIV disease.