[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) is a common sexually transmitted agent that causes anogenital cancer and precancer lesions that have an inflammatory infiltrate, may be friable and bleed. Our aim was to determine the association between anal HPV infection and HIV acquisition.
A prospective cohort study.
We recruited 1409 HIV-negative men who have sex with men from a community-based setting in Boston, Denver, New York and San Francisco. We used Cox proportional hazards regression modeling and assessed the independent association of HPV infection with the rate of acquisition of HIV infection.
Of 1409 participants contributing 4375 person-years of follow-up, 51 HIV-seroconverted. The median number of HPV types in HPV-infected HIV-seroconverters was 2 (interquartile range 1-3) at the time of HIV seroconversion. After adjustment for sexual activity, substance use, occurrence of other sexually transmitted infections and demographic variables, there was evidence (P = 0.002) for the effect of infection with at least two HPV types (hazard ratio 3.5, 95% confidence interval 1.2-10.6) in HIV seroconversion.
Anal HPV infection is independently associated with HIV acquisition. Studies that incorporate high-resolution anoscopy to more accurately identify HPV-associated disease are needed to determine the relationship between HPV-associated disease and HIV seroconversion.
Full-text · Article · May 2009 · AIDS (London, England)
[Show abstract][Hide abstract] ABSTRACT: To understand the extent of immune dysregulation in primary HIV infection (PHI) and the impact of antiretroviral therapy (ART) on restoring these abnormalities, we longitudinally evaluated 52 subjects (Acute-Treated (AT); Early-Treated (ET); Early Untreated (EU)) for markers of activation, proliferation, and function on T cells. ET and AT patients differed by 0.54 log viral load (VL) at baseline but did not differ thereafter by more than 0.34 log10 VL. AT subjects had higher CD8(+) T cell counts and expression of markers indicative of CD8(+) T cell activation (CD38), and proliferation (Ki67), at baseline, than ET subjects but were not different 48 weeks post-ART. Although acute PHI is marked by higher level of immune activation than early PHI, virologic and immunologic responses were similar post-ART, suggesting that the extent of immunologic recovery is not negatively impacted by a delay of treatment beyond the acute stage of disease.
Full-text · Article · Jan 2008 · Clinical Immunology
[Show abstract][Hide abstract] ABSTRACT: Over the past 60 years, Neisseria gonorrhoeae has acquired clinically significant resistance to sulfonamides, tetracyclines, penicillins, and ciprofloxacin.
To determine U.S. trends in the prevalence of antimicrobial resistance of N. gonorrhoeae from 1988 to 2003.
16-year, multisite, sentinel surveillance for gonococcal isolate susceptibility through the Gonococcal Isolate Surveillance Project (GISP).
Sexually transmitted disease clinics in 37 cities.
Male patients with a total of 82,064 episodes of urethral gonorrhea.
Primary outcome measures included percentage of gonococcal isolates resistant to antimicrobials used to treat gonorrhea, percentage of patients treated with specific antimicrobials for gonorrhea, and trends of these measures over time.
The median age of patients was 26 years, and 74.1% of patients were African American. The proportion of men treated with penicillins for gonorrhea declined from 39.5% in 1988 to 0% in 1994, while the proportion of those receiving fluoroquinolone treatment increased from 0% in 1988 to 42.0% in 2003. Penicillin resistance peaked at 19.6% in 1991, then declined to 6.5% in 2003. Tetracycline resistance peaked at 25.8% in 1997 and declined to 14.4% in 2003. The first fluoroquinolone-resistant isolate was found in 1991. Nationally, 0.4% of isolates were fluoroquinolone-resistant in 1999 and were identified in 39% of GISP cities. By 2003, 4.1% of isolates were fluoroquinolone-resistant and were identified in 70% of GISP cities. Isolates with decreased susceptibility to ceftriaxone, cefixime, azithromycin, and spectinomycin remained rare. In 2001, 3 multidrug-resistant isolates with decreased susceptibility to cefixime were identified.
Sentinel surveillance may not fully reflect trends for all patients with gonorrhea in the United States.
Prevalence of penicillin resistance has declined in the years since gonorrhea treatment with penicillin was discontinued. Fluoroquinolone-resistant N. gonorrhoeae infections continue to increase at a time when fluoroquinolone use has increased. Ongoing nationwide and local antimicrobial susceptibility monitoring is crucial to ensure appropriate treatment of gonorrhea.
Full-text · Article · Aug 2007 · Annals of internal medicine
[Show abstract][Hide abstract] ABSTRACT: Interleukin (IL)-18 generates T helper 1-type immunity and inhibits human immunodeficiency virus type 1 (HIV-1) in primary
cells in vitro. Because IL-18 may participate in HIV- 1 containment, whole-blood IL-18 levels were measured in 20 healthy
control subjects and longitudinally in 28 subjects with early HIV-1 infection. Compared with those in control subjects, IL-18
levels were higher during early HIV-1 infection, and IL-18 levels predicted reduced CXCR4 HIV-1 coreceptor expression and
diminished interferon (IFN)-γ levels. By contrast, a direct association between IL-18 and IFN-γ levels was observed in blood
stimulated with lipopolysaccharide. During early HIV-1 infection, IL-18 may regulate HIV-1 coreceptor expression and have
Preview · Article · Apr 2007 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background: The two remaining first-line treatment options for gonorrhea include the oral fluoroquinolones and an injectable cephalosporin. Quinolone resistant Neisseria gonorrhoeae (QRNG) has increased substantially in the last 5 years. If resistance to the quinolones continues to increase, the use of this class of drugs will not be recommended, leaving only an injectable drug as a first-line treatment option.
Methods: The Gonococcal Isolate Surveillance Project (GISP) is a sentinel surveillance project that includes the first 25 male urethral gonococcal isolates obtained each month from STD clinics in 25-30 cities in the U.S. Antimicrobial susceptibilities are determined by agar plate dilution testing and demographic/clinical data are abstracted from medical records.
Results: In 2000, the prevalence of QRNG in GISP was 0.35%, with isolates identified in 6/25 GISP sites; all sites with QRNG were on the west coast or in Hawaii. By 2005, the prevalence of QRNG increased to 9.4%, with resistant isolates identified in 25/27 GISP sites. While the prevalence of QRNG among men who have sex with men (MSM) has increased rapidly from 0.43% in 2000 to 29% in 2005, the prevalence among heterosexuals has also increased steadily from 0.37% in 2000 to 3.9% in 2005.
Conclusions: While the use of fluoroquinolones among MSM is no longer recommended, the prevalence of QRNG among heterosexuals remains low enough in most areas to allow fluoroquinolones to remain an acceptable treatment option in those locales. They are unlikely to remain a treatment option for gonorrhea in the U.S. much longer. Other drugs should be studied as alternative treatment options.
[Show abstract][Hide abstract] ABSTRACT: Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.
No preview · Article · Jun 2005 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Infection with human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In the United States, the incidence of anal cancer among men who have sex with men (MSM) is higher than the incidence of cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are anal cancer precursors comprising low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence of cervical cancer precursor lesions peaks at around 30 years of age. The age-related prevalence of ASILs in HIV-negative MSM is unknown.
We conducted a cross-sectional analysis of the prevalence and determinants of ASILs in 1262 HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology and behavioral data were obtained. Anal HPV infection status was assessed by polymerase chain reaction. Independent predictors of ASILs were identified using logistic regression. All statistical tests were two-sided.
The prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change with age. In a multivariable analysis, the risk of LSILs was associated with having more than five male receptive anal sex partners (P = .03), any use of poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1 to 2.5; P = .03] or use of injection drugs two or more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277; P = .03], older age at first receptive anal intercourse (P = .004), and infection with a greater number of HPV types (P < .001 for linear trend). The risk of HSILs was associated with any anal HPV infection (OR = 3.2, 95% CI = 1.1 to 9.4; P = .039) and infection with an increasing number of HPV types (P < .001 for linear trend).
Sexually active HIV-negative MSM in all age groups have a high prevalence of ASILs, possibly reflecting their ongoing sexual exposure to HPV.
Full-text · Article · Jun 2005 · Journal of the National Cancer Institute
[Show abstract][Hide abstract] ABSTRACT: To meet their sexually transmitted infection (STI) control mission, STI clinics most often offer services at no or minimal cost to clients. However, there is little knowledge about the effects of charging service fees on clinic attendance and STI identification. As a result of budget shortfalls, a clinic fee of 15 US dollars for Denver residents (up to 65 US dollars for nonresidents) was introduced in the Denver Metro Health (STI) Clinic (DMHC) in December 2002. We evaluated the effects of the fee on clinic utilization and diagnosed Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections.
Using the DMHC computerized medical record system, we compared clinic visits and CT/GC diagnoses between the first 3 quarters of 2002 and 2003. We also compared CT/GC cases reported by DMHC with those reported by other Denver providers during 2002 and 2003.
Compared with 2002, there were 3250 fewer visits (-28.5%) to DMHC in 2003 with no variance across quarters. CT diagnoses declined by 427 cases (-28.1%), disproportionately affecting women (-40%) and those under 20 (-42%). In addition, there were 332 fewer GC diagnoses (-38.1%) with no clear demographic preponderance. Although there were some decreases in non-DMHC CT/GC reports, the ratio of DMHC to non-DMHC reports declined from 0.42 to 0.33 (-21.4%) for CT and from 0.94 to 0.61 (-35.1%) for GC.
Even a modest fee for service appears to have a major impact on the use of STI clinic services and may result in a significant effect on the ability to diagnose CT/GC infections, especially among those at highest risk.
[Show abstract][Hide abstract] ABSTRACT: A vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection.
A double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2 : 1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months.
A total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, -17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n=247) and nonwhite (VE, 47%; n=914) volunteers (P=.10, adjusted for multiple subgroup comparisons).
There was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches.
Preview · Article · Apr 2005 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background. A vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection. Methods. A double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2:1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months. Results. A total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, -17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n = 247) and nonwhite (VE, 47%; n = 914) volunteers (P = .10, adjusted for multiple subgroup comparisons). Conclusions. There was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches.
[Show abstract][Hide abstract] ABSTRACT: In the United States, anal cancer in men who have sex with men (MSM) is more common than cervical cancer in women. Human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In women, cervical HPV infection peaks early and decreases after the age of 30. Little is known about the age-specific prevalence of anal HPV infection in human immunodeficiency virus (HIV)-negative MSM.
We studied the prevalence and determinants of anal HPV infection in 1218 HIV-negative MSM, 18-89 years old, who were recruited from 4 US cities. We assessed anal HPV infection status by polymerase chain reaction.
HPV DNA was found in the anal canal of 57% of study participants. The prevalence of anal HPV infection did not change with age or geographic location. Anal HPV infection was independently associated with receptive anal intercourse (odds ratio [OR], 2.0; P<.0001) during the preceding 6 months and with >5 sex partners during the preceding 6 months (OR, 1.5; P<.0001).
Urban, HIV-negative MSM have a stable, high prevalence of anal HPV infection across all age groups. These results differ substantially from the epidemiologic profile of cervical HPV infection in women. This may reflect differences between these populations with respect to the number of new sex partners after the age of 30 and may explain the high incidence of anal cancer in MSM.
Preview · Article · Dec 2004 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: To describe recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of a recombinant gp120 HIV vaccine (AIDSVAX B/B).
Volunteers were gay/bisexual men or women at risk for sexually transmitted HIV infection. Recruitment strategies, demographics, and risk factors were assessed. HIV status was determined by standard HIV-1 antibody assays. Seronegative/viremic HIV infection at enrollment was determined using the HIV-1 nucleic acid test.
From June 1998 through October 1999, 5417 of 7185 volunteers screened were enrolled at 61 sites in the United States, Canada, and The Netherlands. Successful recruitment methods included distribution of study information at gay venues, advertising and media coverage, and referrals from volunteers. Most volunteers were altruistically motivated, men (98%), young (median, 36 years), white (83%), well educated (61% college education or more), and at high risk for HIV during the 6 months before enrollment. At baseline, 14 were HIV infected (12 were seronegative but viremic; 2 were seropositive and viremic).
Men and women at high risk for sexually transmitted HIV infection were successfully recruited for the first phase 3 HIV vaccine efficacy trial. Knowledge of recruitment and baseline epidemiologic characteristics of participants in this trial will provide valuable guidance for designing and conducting future trials.
No preview · Article · Dec 2004 · JAIDS Journal of Acquired Immune Deficiency Syndromes
[Show abstract][Hide abstract] ABSTRACT: Alcohol use may increase HIV sexual risk behavior, although findings have varied across study populations and methods. Using event-level data from 1,712 seronegative men who have sex with men, the authors tested the hypothesis that social context would moderate the effect of alcohol consumption on unprotected anal sex (UAS). For encounters involving a primary partner, rates of UAS did not vary as a function of alcohol use. However, consumption of 4 or more drinks tripled the likelihood of UAS for episodes involving a nonprimary partner. Thus, the effects of alcohol vary according to the context in which it is used. Interventions to reduce substance-related risk should be tailored to the demands of maintaining sexual safety with nonprimary partners.
No preview · Article · Oct 2004 · Health Psychology
[Show abstract][Hide abstract] ABSTRACT: Prior reports associating substance use with sexual risk behavior have generally used summary measures and have not adjusted for participants' background levels of substance use. In this 1999-2001 US study (the EXPLORE study), the authors determined whether substance use during sex was independently associated with sexual risk during recent sexual episodes, as reported by 4,295 human immunodeficiency virus-negative men who have sex with men. The main outcome measure was serodiscordant unprotected anal sex (SDUA). The influence of participant-level characteristics was examined by using repeated-measures logistic models. In assessing the influence of episode-level predictors on SDUA, the influence of participant-level characteristics, including 6-month substance use, was removed by using conditional logistic regression, in effect making each participant his own control. The authors also adjusted for partner characteristics. Eleven percent of participants reported heavy alcohol use, 37% used poppers, 19% sniffed cocaine, and 13% used amphetamines. In the participant-level analysis, use of poppers, amphetamines, and sniffed cocaine as well as heavy alcohol use in the prior 6 months were independently associated with SDUA. In the conditional analysis, consumption of > or = 6 alcoholic drinks or use of poppers, amphetamines, or sniffed cocaine just before or during sex was independently associated with SDUA. The authors concluded that programs aimed at preventing human immunodeficiency virus transmission should emphasize the influence of substance use during sex on increased risk behavior.
Full-text · Article · Jun 2004 · American Journal of Epidemiology
[Show abstract][Hide abstract] ABSTRACT: We describe the prevalence of risk behaviors at baseline among men who have sex with men (MSM) who were enrolled in a randomized behavioral intervention trial conducted in 6 US cities.
Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year.
Among 4295 men, 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months. Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 nonprimary partner. Drug and alcohol use were significantly associated with unprotected anal sex.
Our findings support the continued need for effective intervention strategies for MSM that address relationship status, serostatus of partners, and drug and alcohol use.
Full-text · Article · Jul 2003 · American Journal of Public Health
[Show abstract][Hide abstract] ABSTRACT: Recent increases in rates of sexually transmitted diseases (STDs) and decreases in safe sex behaviors among men who have sex with men (MSM) in several American and European cities have been noted by researchers. It has been suggested that these trends are the result of perceptions that HIV/AIDS is less serious because of the availability of highly active antiretroviral therapy (HAART).
The goal of the study was to examine trends in STD rates and risk behaviors among MSM and men who have sex with women (MSW) visiting a public STD clinic in Denver and to determine whether there is an ecological association with the availability of HAART.
This is a two-part retrospective analysis of male visits to the Denver Metro Health Clinic (DMHC). The first part describes gonorrhea and early (primary and secondary) syphilis trends among MSM between 1982 and 2001. For the second part, data were grouped into two 6-year time periods to represent pre-HAART and post-HAART time frames, 1990 to 1995 and 1996 to 2001.
Gonorrhea and early syphilis cases among MSM declined precipitously between 1982 and 1988 and then stabilized at low rates. The proportion of male visits to the clinic made by MSM decreased from 14.1% in 1990 to 7.2% in 1995 and then increased to 13.0% in 2001. Gonorrhea positivity rates among MSM increased after 1995 and were significantly higher in the period 1996 to 2001 (12.9%) than in the period 1990 to 1995 (8.1%; P<0.0001). Conversely, gonorrhea rates among MSW dropped from 11.2% in the first period to 6.9% in the second (P<0.0001). Among MSM known to be HIV-infected, gonorrhea rates increased from 11.6% in the first time period to 24.0% in the second period (P<0.0001). Reports of anal sex among MSM increased from 64.4% to 70.9% (P<0.0001). Reporting more than one sex partner increased for MSM from 65.2% to 70.3% (P<0.0001), but it significantly decreased from 52.6% to 46.2% for MSW (P<0.0001). No or inconsistent condom use increased from 60.9% to 63.0% for MSM (P=NS) and decreased from 85.1% to 82.4% among MSW (P<0.0001).
These trends appear to reflect a change toward higher risk-taking behaviors among MSM but not MSW since the time HAART became available and raise concerns about the potential for increased HIV transmission in this group.
[Show abstract][Hide abstract] ABSTRACT: We describe the intervention tested in EXPLORE, an HIV prevention trial aimed at men who have sex with men (MSM), and test the empirical basis of the individually tailored intervention.
Data on participants' self-efficacy, communication skills, social norms, and enjoyment of unprotected anal intercourse were examined in relation to sexual risk. Combinations of these factors, together with alcohol use and noninjection drug use, were also examined.
The individual factors examined were associated with sexual risk behavior. The cohort was shown to be heterogeneous in regard to the presence of combinations of these risk-related factors.
Baseline data from the EXPLORE study support the efficacy of the individually tailored intervention used.
Full-text · Article · Jul 2003 · American Journal of Public Health
[Show abstract][Hide abstract] ABSTRACT: Prior studies have used Chlamydia trachomatis culture methods to demonstrate both persistence and spontaneous clearance of genital C trachomatis infection.
To further assess the issue of persistence and spontaneous clearance of C trachomatis infection, untreated men and women were evaluated with repeated polymerase chain reaction (PCR) testing.
Ninety four untreated patients with a prior positive C trachomatis PCR test returning to the Denver Metro Sexually Transmitted Disease Clinic were retested by PCR.
The median and range intervals from initial to follow-up testing were 9.0 (2-112) days for men and 10.0 (2-231) days for women. Repeated PCR tests were positive for 29 of 36 men (80.6%) and 45 of 58 women (77.6%). Persistent PCR positivity did not decrease with a longer testing interval. By multivariate analysis, independent predictors of a persistently positive PCR test included nonwhite ethnicity, an interval of more than 3 days since last sexual encounter before the initial test, and an initial PCR optical density value of greater than or equal to 3.0.
In the absence of treatment, a large majority of patients testing positive for C trachomatis by PCR are likely to remain positive for variable periods of time, increasing the risk of transmission and immune-mediated damage. A low initial optical density value and recent sexual contact may be markers for exposure that does not establish infection.
[Show abstract][Hide abstract] ABSTRACT: From 1982–1998, enhanced sentinel surveillance for acute hepatitis B was conducted in 4 counties in the United States to determine
trends in disease incidence and risk factors for infection. During this period, the reported incidence of acute hepatitis
B declined by 76.1 % from 13.8 cases per 100,000 in 1987 to 3.3 cases per 100,000 in 1998. Cases associated with injection
drug use (IDU) decreased by 90.6%, men who have sex with men (MSM) by 63.5%, and heterosexual activity by 50.7%. During 1994–1998,
the most commonly reported risk factor for infection was high-risk heterosexual activity (39.8%) followed by MSM activity
(14.6%) and IDU (13.8%). Over half of all patients (55.5%) reported treatment for a sexually transmitted disease (STD) or
incarceration in a prison or jail prior to their illness, suggesting that more than half of the acute hepatitis B cases might
have been prevented through routine hepatitis B immunization in STD clinics and correctional health care programs.
Preview · Article · Apr 2002 · The Journal of Infectious Diseases