Prevention of sexually transmitted infections in urban communities (Peru PREVEN): a multicomponent community-randomised controlled trial.

BACKGROUND: Previous community-randomised trials of interventions to control sexually transmitted infections (STIs) have involved rural settings, were rarely multicomponent, and had varying results. We aimed to assess the effect of a multicomponent intervention on curable STIs in urban young adults and female sex workers (FSWs). METHODS: In this community-randomised trial, baseline STI screening was done between August, and November, 2002, in random household samples of young adults (aged 18-29 years) and in FSWs in Peruvian cities with more than 50,000 inhabitants. Geographically separate cities were selected, matched into pairs, and randomly allocated to intervention or control groups with an S-PLUS program. Follow-up surveys of random samples were done after 2 years and 3 years. The intervention comprised four modalities: strengthened STI syndromic management by pharmacy workers and clinicians; mobile-team outreach to FSWs for STI screening and pathogen-specific treatment; periodic presumptive treatment of FSWs for trichomoniasis; and condom promotion for FSWs and the general population. Individuals in control cities received standard care. The composite primary endpoint was infection of young adults with Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae, or syphilis seroreactivity. Laboratory workers and the data analyst were masked, but fieldworkers, the Peruvian study team, and participants in the outcome surveys were not. All analyses were done by intention to treat. This trial is registered, ISRCTN43722548. FINDINGS: We did baseline surveys of 15,261 young adults in 24 Peruvian cities. Of those, 20 geographically separate cities were matched into pairs, in each of which one city was assigned to intervention and the other to standard of care. In the 2006 follow-up survey, data for the composite primary outcome were available for 12,930 young adults. We report a non-significant reduction in prevalence of STIs in young adults, adjusted for baseline prevalence, in intervention cities compared with control cities (relative risk 0·84, 95% CI 0·69-1·02; p=0·096). In subgroup analyses, significant reductions were noted in intervention cities in young adult women and FSWs. INTERPRETATION: Syndromic management of STIs, mobile-team outreach to FSWs, presumptive treatment for trichomoniasis in FSWs, and condom promotion might reduce the composite prevalence of any of the four curable STIs investigated in this trial. FUNDING: Wellcome Trust and Burroughs Wellcome Fund, National Institutes of Health, Center for AIDS Research, CIPRA, and USAID-Peru.

Ureaplasma urealyticum is associated with nongonococcal urethritis among men with fewer lifetime sexual partners: a case-control study.

BACKGROUND: Ureaplasmas have been inconsistently associated with nongonococcal urethritis (NGU). We evaluated the association of the newly differentiated species Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) with NGU using 2 separate control groups. METHODS: Case patients were men who attended a sexually transmitted disease (STD) clinic in Seattle, Washington, during the period 2007-2009 with NGU (defined as visible urethral discharge and/or ≥5 polymorphonuclear neutrophils per high-powered field; n = 329). Control subjects were STD clinic attendees (n = 191) and emergency department (ED) attendees (n = 193) without NGU. Polymerase chain reaction assays detected UU and UP in ureaplasma culture-positive urine. Multivariable logistic regression was used to assess the associations of UU and UP with NGU. RESULTS: UU was only marginally associated with NGU in aggregate multivariable analyses, irrespective of control group (adjusted odds ratio [aOR](STD-control), 1.6 [95% confidence interval {CI}, 0.9-2.8]; aOR(ED-control), 1.7 [95% CI, 0.97-3.0]). This association was significantly stronger when analyses were restricted to men with fewer lifetime sex partners (<10 vaginal partners: aOR(STD-control), 2.9 [95% CI, 1.2-6.7]; aOR(ED-control), 3.2 [95% CI, 1.3-7.6]; <5 vaginal partners: aOR(STD-control), 6.2 [95% CI, 1.8-21.0]; aOR(ED-control), 5.2 [95% CI, 1.3-20.2]). UP was not positively associated with NGU overall or among subgroups. CONCLUSIONS: The absence of an association of UU with NGU among men with more lifetime sex partners suggests that adaptive immunity may attenuate the clinical manifestation of UU infection. Similar relationships were not observed with UP, which suggests that it is not a urethral pathogen.

Demographic, behavioral, and clinical characteristics of men with nongonococcal urethritis differ by etiology: a case-comparison study.

BACKGROUND: Nongonococcal urethritis (NGU) is common, yet up to 50% of cases have no defined etiology. The extent to which risk profiles and clinical presentations of pathogen-associated and idiopathic cases differ is largely unknown. METHODS: Urethral swabs and urine specimens were collected from 370 NGU treatment trial participants who sought care at a sexually transmitted disease clinic in Seattle, WA from 2007 to 2009 and had a visible urethral discharge and/or microscopic evidence of urethral inflammation assessed by Gram-stain (≥5 polymorphonuclear leukocytes per high-powered field [PMNs/HPF]). Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV), and Ureaplasma urealyticum (UU) were detected in urine, using nucleic acid amplification tests. Cases negative for all assessed pathogens were considered idiopathic. Bivariate and multivariate analyses identified clinical, sociodemographic, and behavioral factors associated with detection of specific pathogens. RESULTS: After excluding 3 participants with gonococcal infection, pathogens were detected in only 50.7% of the 367 eligible cases: CT in 22.3%, MG in 12.5%, TV in 2.5%, and UU in 24.0%, with multiple pathogens detected in 9.5%. In all, 3.5% of cases were negative for CT, MG, and TV but lacked speciated ureaplasma results. The remaining cases (45.8%) were considered idiopathic. Pathogen detection was associated with young age, black race, risky sexual behaviors, cloudy or purulent discharge, and visible discharge plus≥5 PMNs/HPF. In contrast, idiopathic cases were more likely to report prior NGU, were older and less likely to be black, or have an abnormal urethral discharge on examination, compared to all other cases. These cases were not associated with any high risk behaviors. CONCLUSIONS: NGU is a heterogeneous condition. Pathogen detection was associated with a variety of traditional risk factors and clinical features; whereas, idiopathic cases tended to be diagnosed among lower-risk men.

Non-monogamy and risk of infection with Chlamydia trachomatis and Trichomonas vaginalis among young adults and their cohabiting partners in Peru.

OBJECTIVES: To determine how patterns of non-monogamy influence prevalences of sexually transmitted infections (STIs) in individuals and their cohabitating sex partners. METHODS A 2002 survey in 24 Peruvian cities enrolled men and women aged 18-29 years from random household samples. The cohabiting sex partner of each enrolee was also enrolled until approximately 100 couples per city were recruited. Men provided urine and women vaginal swabs or urine for molecular testing for Chlamydia trachomatis and Trichomonas vaginalis; both genders provided blood for serological testing. RESULTS: Among 2099 females and 2052 males providing specimens and behavioural data, 18.2% of males and 2.5% of females reported non-monogamy during the past year. C trachomatis was detected in 121 females (5.8%) and 80 males (4.1%) and T vaginalis in 87 females (4.2%) and 26 males (1.3%). Multivariate analyses showed that C trachomatis infection in females was significantly associated with her male partner's non-monogamy (OR 2.02, CI 1.32 to 3.08) but not significantly with her own non-monogamy; T vaginalis was associated with her own non-monogamy (OR 3.11, CI 1.25 to 7.73) and with her partner's non-monogamy (OR 2.07, CI 1.26 to 3.42). For males, both C trachomatis (OR 2.17, CI 1.29 to 3.69) and T vaginalis (OR 2.49, CI 1.06 to 5.87) were significantly associated only with his own non-monogamy. CONCLUSIONS: Among cohabiting couples, male non-monogamy was common and was associated with C trachomatis and T vaginalis infection in himself and in his female partner, whereas female non-monogamy was reported infrequently and was significantly associated only with her own T vaginalis infection. Patterns of non-monogamy may guide public health interventions.

Studying complex interactions among determinants of healthcare-seeking behaviours: self-medication for sexually transmitted infection symptoms in female sex workers.

OBJECTIVES: To describe the frequency and determinants of self-medication for symptoms of sexually transmitted infections (STI) in a female sex worker (FSW) population. To present a methodology exploring the best predictors as well as the interactions between determinants of self-medication. METHODS: A cross-sectional survey of 4153 FSW carried out in Peru. The prevalence of self-medication was estimated from the subsample of participants who had experienced symptoms of STI in the past 12 months (n=1601), and used successive logistic regression models to explore the determinants. RESULTS: Self-medication prevalence for a reported symptomatic episode during the past 12 months was 32.1% (95% CI 29.8 to 34.6). It was negatively correlated with work in brothels (adjusted odds ratio (OR) 0.51, 95% CI 0.28 to 0.93; p=0.028) and awareness of STI services available for FSW (adjusted OR 0.49, 95% CI 0.29 to 0.81; p=0.006). Other determinants were organised at different levels of proximity to the outcome creating pathways leading to self-medication. CONCLUSIONS: The importance of the staggered analysis presented in this study resides in its potential to improve the understanding of associations between determinants and, consequently, the targeting of interventions. The awareness of STI services available for FSW increases access to health care, which in turn decreases self-medication. In addition, the sharing of information that takes place between brothel-based FSW was also related to a diminishing prevalence of self-medication. These two main predictors provide an opportunity for prevention programmes, in particular those designed to be led by peers.

Expedited partner therapy: a robust intervention.

BACKGROUND: Expedited partner therapy (EPT) has been shown to reduce the risk of persistent or recurrent gonorrhea and chlamydial infection in heterosexuals, and to increase the proportion of sex partners receiving treatment. The objective of this analysis was to evaluate the consistency of EPT's effect across sociodemographic and behavioral subgroups. METHODS: Subset analyses from a randomized controlled trial compared EPT to standard partner referral (SPR) in sociodemographic and behaviorally defined subgroups. Outcomes included persistent or recurrent infection in study participants and participants' report that their partners received treatment. RESULTS: Reinfection risk was lower among EPT recipients than nonrecipients in 21 of 22 subgroups, with relative risks (RRs) varying from 0.4 to 0.94. Compared to persons receiving SPR, persons receiving EPT were more likely to report that their partners were very likely to have been treated in 33 of 34 subgroups (RRs range, 1.03-1.36). Although EPT reduced the risk of persistent or recurrent infection somewhat more in men (RR, 0.56; 95% CI, 0.3-1.08) than in women (RR, 0.81; 95% CI, 0.61-1.07) and more in persons with gonorrhea (RR, 0.32; 95% CI, 0.13-0.78) than those with chlamydial infection (RR, 0.82; 95% CI, 0.63-1.07), the RR of partners being treated associated with EPT was similar in men (RR, 1.21; 95% CI, 1.05-1.39) and women (RR, 1.18; 95% CI, 1.10-1.27), and also in persons with gonorrhea (RR, 1.33; 95% CI, 0.80-2.23) and chlamydial infection (RR, 1.33; 95% CI, 1.07-1.66). CONCLUSIONS: In this study, EPT is shown to be superior to SPR across a wide spectrum of sociodemographic and behaviorally defined subgroups.

Differential association of ureaplasma species with non-gonococcal urethritis in heterosexual men.

OBJECTIVE: To assess the role of Ureaplasma urealyticum and Ureaplasma parvum in patients with non-gonococcal urethritis (NGU) using specimens from a previously reported study of NGU. METHODS: Species-specific PCR assays for U urealyticum and U parvum were used to detect these organisms in specimens from men enrolled in a case-control study based in a Seattle STD clinic in order to evaluate their association with NGU. Urethritis was defined by clinical examination and the presence of inflammation on Gram stained smear. Controls had normal examination findings and no evidence of inflammation on Gram stain smear or by the leucocyte esterase test. RESULTS: U urealyticum was detected in 26% (31/119) of cases and 16% (19/117) of controls, resulting in an association with NGU (adjusted odds ratio (aOR)=2.3, 95% CI 1.04 to 4.9) after adjusting for age, race, history of prior urethritis and other NGU pathogens (Chlamydia trachomatis, Mycoplasma genitalium). The association of U urealyticum and NGU was strongest in white men <28 years of age (OR=5.4, 95% CI 1.3 to 22.2). U parvum was detected in 14% (17/119) cases and 31% (36/117 controls) and thus was negatively associated with NGU (aOR=0.4, 95% CI 0.2 to 0.8). The prevalence of U urealyticum (16%) in controls was higher than that of C trachomatis (3.4%) or M genitalium (4.3%, p<0.05, each comparison). CONCLUSIONS: Unlike U parvum, U urealyticum was associated with urethritis. The strong effect in younger white men and high rates in controls may suggest variability in virulence among U urealyticum strains or in host innate or acquired immunity.

Estimating duration in partnership studies: issues, methods and examples.

BACKGROUND AND OBJECTIVES: Understanding the time course of sexual partnerships is important for understanding sexual behaviour, transmission risks for sexually transmitted infections (STI) and development of mathematical models of disease transmission. STUDY DESIGN: The authors describe issues and biases relating to censoring, truncation and sampling that arise when estimating partnership duration. Recommendations for study design and analysis methods are presented and illustrated using data from a sexual-behaviour survey that enrolled individuals from an adolescent-health clinic and two STD clinics. Survey participants were queried, for each of (up to) four partnerships in the last 3 months, about the month and year of first sex, the number of days since last sex and whether partnerships were limited to single encounters. Participants were followed every 4 months for up to 1 year. RESULTS: After adjustment for censoring and truncation, the estimated median duration of sexual partnerships declined from 9 months (unadjusted) to 1.6 months (adjusted). Similarly, adjustment for censoring and truncation reduced the bias in relative risks for the effect of age in a Cox model. Other approaches, such as weighted estimation, also reduced bias in the estimated duration distribution. CONCLUSION: Methods are available for estimating partnership duration from censored and truncated samples. Ignoring censoring, truncation and other sampling issues results in biased estimates.

Sexually transmitted infections among HIV-1-discordant couples.

INTRODUCTION: More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS: HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS: Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01), and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01) and those with low education (OR = 3.00; P<0.01). Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01). CONCLUSIONS: Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.

Mosaic penicillin-binding protein 2 in Neisseria gonorrhoeae isolates collected in 2008 in San Francisco, California.

Using a real-time PCR assay specific for a mosaic penA allele that has been associated with oral cephalosporin resistance in Asia, 54 available Neisseria gonorrhoeae isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic penA gene by real-time PCR. DNA sequencing revealed two mosaic penA alleles (SF-A and SF-B). Isolates with SF-A and SF-B alleles possessed elevated MICs for the oral cephalosporins cefpodoxime and cefixime.

Characteristics of HIV-1 discordant couples enrolled in a trial of HSV-2 suppression to reduce HIV-1 transmission: the partners study.

BACKGROUND: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort. METHODS: HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count >or=250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed. RESULTS: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2-9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (<5%), except for Trichomonas vaginalis in 14% of HIV-1 infected women. Median baseline CD4 count for HIV-1 infected participants was 462cells/mcL and median HIV-1 plasma RNA was 4.2 log(10) copies/mL. After adjusting for age and African region, correlates of HIV-1 RNA level included male gender (+0.24 log(10) copies/mL; p<0.001) and CD4 count (-0.25 and -0.55 log(10) copies/mL for CD4 350-499 and >500 relative to <350, respectively, p<0.001). CONCLUSIONS: The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00194519.

HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men.

OBJECTIVES: Suppressive herpes simplex virus (HSV) therapy can decrease plasma, cervical, and rectal HIV-1 levels in HIV-1/HSV-2 co-infected persons. We evaluated the effect of HSV-2 suppression on seminal HIV-1 levels. DESIGN: Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2 men who have sex with men (MSM) in Lima, Peru, with CD4 >200 cells/microl randomly received valacyclovir 500 mg twice daily or placebo for 8 weeks, then the alternative regimen for 8 weeks after a 2-week washout. Peripheral blood and semen specimens were collected weekly. Anogenital swab specimens for HSV DNA were self-collected daily and during clinic visits. METHODS: HIV-1 RNA was quantified in seminal and blood plasma by TaqMan real-time polymerase chain reaction (RT-PCR) or Roche Amplicor Monitor assays. HSV and seminal cytomegalovirus (CMV) were quantified by RT-PCR. Linear mixed models examined differences within participants by treatment arm. RESULTS: Median CD4 cell count of participants was 424 cells/microl. HIV-1 was detected in 71% of 231 semen specimens. HSV was detected from 29 and 4.4% of swabs on placebo and valacyclovir, respectively (P < 0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo; P = 0.04). Seminal HIV-1 quantity was 0.25 log10 copies/ml lower [95% confidence interval (CI) -0.40 to -0.10; P = 0.001] during the valacyclovir arm compared with placebo, a 44% reduction. CD4 cell count (P = 0.32) and seminal cellular CMV quantity (P = 0.68) did not predict seminal plasma HIV-1 level. CONCLUSIONS: Suppressive valacyclovir reduced seminal HIV-1 levels in HIV-1/HSV-2 co-infected MSM not receiving ART. The significance of this finding will be evaluated in a trial with HIV-1 transmission as the outcome.

Prevalence and correlates of human herpesvirus 8 infection among Peruvian men who have sex with men.

BACKGROUND: Infection with human herpesvirus 8 (HHV-8) is common among men who have sex with men (MSM) in North America and Europe and is also found to be endemic in some regions of South America. Little is known about HHV-8 prevalence and its correlates among MSM in the Andean region. METHODS: We assessed HHV-8 seroprevalence among 497 MSM recruited for the 2002 Peruvian HIV sentinel surveillance program using a combined HHV-8 enzyme immunoassay and immunofluorescence assay algorithm. Logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) to determine the association between selected covariates and HHV-8 seropositivity. RESULTS: One hundred thirty-one (66.5%, 95% CI 63.1% to 69.9%) of 197 HIV-infected and 80 (26.7%, 95% CI 24.4% to 29.0%) of 300 HIV-uninfected MSM had serologic evidence of HHV-8 infection. Factors independently associated with HHV-8 infection were education<12 years (OR 1.7, 95% CI 1.1 to 2.7), anal receptive sex with the last partner (OR 2.0, 95% CI 1.2 to 3.3), self-reported sexually transmitted infection symptoms during the last year (OR 1.9, 95% CI 1.2 to 3.0), coinfection with HIV (OR 4.2, 95% CI 2.8 to 6.4) and chronic hepatitis B (OR 4.9, 95% CI 1.5 to 15.8). MSM with long-standing HIV infection were more likely to have serologic evidence of HHV-8 infection when compared with men with recently acquired HIV (OR 3.8, 95% CI 1.7 to 9.1). CONCLUSIONS: HHV-8 infection is common among both HIV-infected and HIV-negative MSM in Lima, Peru. HHV-8 seropositivity is correlated with anal receptive sex, self-reported sexually transmitted infection symptoms, and HIV infection among these MSM and thus seems to be sexually transmitted. HHV-8 infection seems to be acquired after HIV infection, suggesting that future studies should evaluate the mode of HHV-8 transmission and prevention strategies among HIV-uninfected MSM.

Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial.

A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (-0.26 log10 copies/mL, a 45% decrease [P < .001]), as was cervical HIV-1 level (-0.35 log10 copies/swab, a 55% decrease [P < .001]). Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression.

Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is common among human immunodeficiency virus (HIV)-infected persons, and HSV reactivation increases plasma and genital HIV-1 levels. We studied HIV-1 levels during HSV suppression in coinfected persons in a placebo-controlled crossover trial. METHODS: Twenty antiretroviral therapy (ART)-naive HIV-1/HSV-2-seropositive men who have sex with men in Lima, Peru, with CD4 cell counts >200 cells/ microL were randomized to receive either valacyclovir at 500 mg twice daily or placebo for 8 weeks, after which they underwent a 2-week washout period and then received the alternative regimen for 8 weeks. Specimens included daily anogenital swabs (for HSV DNA polymerase chain reaction [PCR]), thrice weekly rectal mucosal secretions (for HIV-1 RNA and HSV DNA PCR) obtained by anoscopy, and weekly plasma (for HIV-1 RNA PCR). Outcomes were rectal and plasma HIV-1 RNA levels by treatment arm. RESULTS: HIV-1 was detected in 73% of 844 rectal and 99% of 288 plasma specimens. HSV was detected in 29% and 4% of mucocutaneous specimens obtained during placebo and valacyclovir administration, respectively (P<.001). Valacyclovir resulted in a 0.16 (95% confidence interval [CI], 0.07-0.25; P=.0008; 33% decrease) log(10) copies/mL lower mean within-subject rectal HIV-1 level and a 0.33 (95% CI, 0.23-0.42; P<.0001; 53% decrease) log(10) copies/mL lower plasma HIV-1 level, compared with values for placebo. CONCLUSIONS: Valacyclovir significantly reduces rectal and plasma HIV-1 levels in HIV-1/HSV-2-coinfected men. HSV suppression may provide clinical benefits to persons not receiving highly active ART as well as public health benefits.

Antimicrobial resistance for Neisseria gonorrhoeae in the United States, 1988 to 2003: the spread of fluoroquinolone resistance.

BACKGROUND: Over the past 60 years, Neisseria gonorrhoeae has acquired clinically significant resistance to sulfonamides, tetracyclines, penicillins, and ciprofloxacin. OBJECTIVE: To determine U.S. trends in the prevalence of antimicrobial resistance of N. gonorrhoeae from 1988 to 2003. DESIGN: 16-year, multisite, sentinel surveillance for gonococcal isolate susceptibility through the Gonococcal Isolate Surveillance Project (GISP). SETTING: Sexually transmitted disease clinics in 37 cities. PATIENTS: Male patients with a total of 82,064 episodes of urethral gonorrhea. MEASUREMENTS: 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. RESULTS: 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. LIMITATION: Sentinel surveillance may not fully reflect trends for all patients with gonorrhea in the United States. CONCLUSIONS: 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.

Evaluation of a population-based program of expedited partner therapy for gonorrhea and chlamydial infection.

OBJECTIVE: To evaluate a partner notification program for gonorrhea and chlamydial infection that involves communitywide access to free patient-delivered partner therapy (PDPT) and use of case-report forms to triage patients to receive partner notification assistance. METHODS: We evaluated program components in randomly selected cases and compared outcomes before and after program institution. RESULTS: Following institution of the program, the percentage of cases who received PDPT from their diagnosing clinician increased from 5.6% to 16% (adjusted OR 3.2, 2.5-4.1). Among randomly selected cases, those referred to the health department via the case-report form were significantly more likely than nonreferred cases to have untreated sex partners (76% vs. 35%, OR 6.0, 95% CI 4.5-8.0), to accept PDPT from the health department (36% vs. 14%, 3.3, 95% CI 2.4-4.7), and to request that health department staff notify a partner for them (11% vs. 3%, OR 3.5, 95% CI 1.8-6.7). The percentage of cases classified as having all of their partners treated increased from 39% to 65% concurrent with institution of the program. CONCLUSIONS: A public health program that promotes routine use of PDPT and referral of selected patients for partner notification assistance appears to have improved partner notification outcomes.

Real-time PCR assay for detection of quinolone-resistant Neisseria gonorrhoeae in urine samples.

A need exists for the development of applicable surveillance tools to detect fluoroquinolone-resistant Neisseria gonorrhoeae (QRNG) in urine samples. We describe here a real-time PCR assay for detecting mutations in the Ser91 codon of the gyrA gene of N. gonorrhoeae in urine specimens. We tested 96 urine samples collected along with Gonorrhea Isolate Surveillance Project (GISP) urethral swab samples and compared the results with matched MICs of ciprofloxacin, as reported by the regional GISP laboratory. We then tested 100 urine specimens, known to be gonorrhea positive by nucleic acid amplification testing, provided by females to challenge the real-time PCR assay with urine specimens containing potentially less target DNA content than specimens from symptomatic males. With an MIC threshold of 0.125 mug of ciprofloxacin/ml, our assay correctly identified resistance in 41 of 44 (93.2%; 95% confidence interval [CI] = 81.3 to 98.6%) corresponding resistant culture specimens and correctly identified 51 of 51 (100%; 95% CI = 93.0 to 100%) susceptible specimens. One specimen did not amplify. The assay successfully amplified the gyrA amplicon and determined a susceptibility genotype in 72 of 100 (72%) urine specimens collected from female patients. We developed an assay for detecting QRNG in urine specimens that correlated well with MIC results of cultured specimens and had moderate sensitivity with urine specimens. This methodology might fulfill the need for a QRNG detection system for urine specimens, a useful characteristic in the age of nucleic acid amplification testing for gonococcal infection.

Partner-specific sexual behavioral differences between phase 3 HIV vaccine efficacy trial participants and controls: Project VISION.

OBJECTIVE: To assess and compare sexual behaviors using partner-specific data between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine efficacy trial and a control group. METHODS: HIV-negative MSM from an HIV vaccine trial (n = 525) and controls (n = 732) were recruited by similar strategies and interviewed about behaviors with the 3 most recent partners in the past 6 months, obtained by audio computer-assisted self-interview (A-CASI). RESULTS: Vaccine trial participants were more likely than controls to report an HIV-positive partner (24.7% and 14.1%, respectively) or an HIV-positive primary partner (16.1% and 6.8%, respectively) and were less likely to report occasional or single-time partners of unknown HIV status (51.6% and 63.2%, respectively; P < 0.05 for each comparison). Vaccine trial participants more often reported receptive unprotected anal intercourse (UAI) during their last sexual encounter with an HIV-positive partner (adjusted odds ratio [OR] = 2.7, 95% confidence interval [CI]: 1.0 to 7.9). Most believed their HIV-positive partners were receiving antiretroviral treatment (ART), however, and after adjustment for perceived ART use, the association between vaccine study participation and receptive UAI with an HIV-positive partner was not significant. CONCLUSIONS: High-risk sexual behavior was reported by many VAX004 participants and controls. Differences between vaccine trial and control participants in the highest risk per contact behavior, receptive UAI with HIV-positive partners, was partly accounted for by perceived ART use. Partner level data are useful in refining risk assessment, which is important in the evaluation of HIV vaccine and other prevention trials.

Linking HIV and antiretroviral drug resistance surveillance in Peru: a model for a third-generation HIV sentinel surveillance.

BACKGROUND: HIV drug resistance surveillance is limited by recruitment and selection bias and by limited information regarding HIV incidence rates, secondary resistance, and treatment prevalence. METHODS: A second-generation HIV sentinel surveillance among men who have sex with men (MSM), regardless of prior history of HIV screening, serostatus, or treatment, was conducted in Peru in 2002. Recent HIV infection was estimated using sensitive/less sensitive enzyme immunoassay testing. Genotypic resistance testing was performed. RESULTS: HIV prevalence was 13.9% (456 HIV positive of 3280 participants). HIV incidence was estimated to be 5.1 per 100 person-years (95% confidence interval: 3.1-8.3). Among 143 MSM who were aware of their HIV infection before testing, only 20 (14.0%) were receiving antiretrovirals (ARV). Mutations conferring ARV resistance were found in 12 (3.3%) of 359 treatment-naive and 5 (31.3%) of 16 treatment-experienced participants with successful genotyping. One recently infected man from Lima demonstrated 3-class multidrug resistance. The most frequently observed mutations in treatment-naive, chronically infected persons from Lima were M184V (1.7%), D30N (1.3%), L90M (1.3%), and L10I (1.3%). CONCLUSIONS: The prevalence of ARV resistance among treatment-naive MSM in Peru is low, reflecting limited access to treatment before 2004, and contrasts with the history of ARV treatment in developed countries, where high levels of nucleoside reverse transcriptase inhibitor resistance occurred before introduction of highly active antiretroviral therapy. Linking ARV resistance and HIV sentinel surveillance in developing settings is feasible and should be considered in third-generation HIV sentinel surveillance programs.