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.

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.

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.

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.

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.

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.

Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection.

BACKGROUND: Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission. METHODS: We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment. RESULTS: Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner. CONCLUSIONS: Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection.

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.

Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon, California, Washington, and Hawaii. Faropenem retained its potency against these recent clinical strains and also quinolone-resistant strains from Japan (MIC90, < or =0.25 microg/mL). In summary, the excellent activity of faropenem against the gonococcal strains analyzed irrespective of the resistance phenotype, along with its beta-lactamase stability, makes it an ideal contender for further development as an oral beta-lactam agent to treat uncomplicated gonococcal infections due to strains emerging with resistant to penicillins, tetracyclines, and fluoroquinolones.

Sexually transmitted diseases and human immunodeficiency virus-discordant partnerships among men who have sex with men.

Sexually active men who have sex with men (MSM) at 5 Seattle clinics were assessed for bacterial sexually transmitted diseases (STDs), human immunodeficiency virus (HIV)-discordant partnerships, sexual behavior, and drug use. Of the HIV-positive men, 45% reported having HIV-negative sex partners and 42% reported having sex partners with unknown serostatus during the past 2 months, whereas 14% and 57% of HIV-negative men reported having HIV-positive and unknown-serostatus sex partners, respectively. Correlates of sex partners with unknown serostatus were recruiting sex partners at bathhouses or parks. Gonorrhea, chlamydia, or syphilis was diagnosed in 12% of HIV-positive and 13% of HIV-negative MSM, and the rates did not differ between men with HIV-concordant and HIV-discordant partnerships. High prevalences of bacterial STDs and HIV-discordant partnerships emphasize the need for interventions to foster serostatus discussion, condom use, fewer anonymous partners, and STD screening.

Predicting chlamydial and gonococcal cervical infection: implications for management of cervicitis.

OBJECTIVE: To define utility of age and cervical findings in predicting infection with Chlamydia trachomatis and Neisseria gonorrhoeae among women universally tested for both infections, and to assess the independent contribution of Gram stain (GS) smear of endocervical secretions. METHODS: Visits by women to Seattle sexually transmitted diseases clinics from 1995 through 1999 were retrospectively reviewed. All women had endocervical GS and cultures for C trachomatis and N gonorrhoeae performed. Predictive values of age, cervical signs, and inflammation on GS (more than 30 polymorphonuclear leukocytes per 1000x field) were calculated. RESULTS: Among 6230 women, prevalence of C trachomatis and N gonorrhoeae was 6.9% and 2.1%, respectively; 520 women (8.3%) had either organism detected. Age, cervical signs (mucopus, induced bleeding), and inflammation on endocervical GS were independently associated with infection. However, the positive predictive value (PPV) of any cervical finding for infection was less than 19% in women 25 years and older. Inflammation on endocervical GS was the sole indicator of infection in 79 of 520 (15%) infections, but was insensitive in the absence of mucopurulent cervicitis (sensitivity, 26%; PPV, 21%). CONCLUSION: Cervical signs suggesting chlamydial or gonococcal infection have higher positive predictive value (PPV) in younger women. The PPV of inflammation on endocervical GS is too low to recommend its use to direct empiric treatment in the absence of mucopurulent cervicitis, especially in women 25 years and older. Further, its low sensitivity in detecting infection in women without mucopurulent cervicitis does not justify routine use. Signs suggesting mucopurulent cervicitis should be interpreted in the context of age, and empiric treatment may not be indicated in women aged 25 years and older.

Failure of family-planning referral and high interest in advanced provision emergency contraception among women contacted for STD partner notification.

BACKGROUND: Few data are available on the risk of unintended pregnancy in women with STD or how contraceptive services can be integrated into STD control activities. OBJECTIVE: To define the risk for unintended pregnancy and assess the effectiveness of family-planning (FP) referral and interest in advanced provision emergency contraception (APEC) among women with gonorrhea or chlamydial infection. METHODS: Female participants in a randomized trial of different approaches to partner notification were interviewed, offered referral for FP services and asked if they would want APEC. RESULTS: Among participants ages 14-24, the observed past pregnancy rate and age-adjusted anticipated past pregnancy rate were, respectively, 196 and 72 per 1000 women-years. Of 474 nonpregnant participants who did not desire pregnancy, 127 (34%) were using no contraception or condoms alone, of whom 8 (6%) requested a FP appointment and 81% wanted APEC. CONCLUSIONS: Women treated for STD are at high-risk for unintended pregnancy. Although referral for FP was ineffective, interest in APEC was very high.

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.

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.

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.