What Is the Optimal Time to Retest Patients With a Urogenital Chlamydia Infection? A Randomized Controlled Trial.

BACKGROUND: Chlamydia trachomatis is a common, often recurring sexually transmitted infection, with serious adverse outcomes in women. Current guidelines recommend retesting after a chlamydia infection, but the optimum timing is unknown. We assessed the optimal retest interval after urogenital chlamydia treatment. METHODS: A randomized controlled trial among urogenital chlamydia nucleic acid amplification test positive heterosexual clients of the Amsterdam sexually transmitted infection clinic. After treatment, patients were randomly assigned for retesting 8, 16, or 26 weeks later. Patients could choose to do this at home (and send a self-collected sample by mail) or at the clinic. Retest uptake and chlamydia positivity at follow-up were calculated. RESULTS: Between May 2012 and March 2013, 2253 patients were included (45% men; median age, 23 years; interquartile range, 21-26). The overall uptake proportion within 35 weeks after the initial visit was significantly higher in the 8-week group (77%) compared with the 16- and 26-week groups (67% and 64%, respectively, P < 0.001), and the positivity proportions among those retested were comparable (P = 0.169). The proportion of people with a diagnosed recurrent chlamydia infection among all randomized was similar between the groups (n = 69 [8.6%], n = 52 [7.4%], and n = 69 [9.3%]; P = 0.4). CONCLUSIONS: Patients with a recent urogenital chlamydia are at high risk of recurrence of chlamydia and retesting them is an effective way of detecting chlamydia cases. We recommend inviting patients for a re-test 8 weeks after the initial diagnosis and treatment.

The Cervicovaginal Microbiota in Women Notified for Chlamydia trachomatis Infection: A Case-Control Study at the Sexually Transmitted Infection Outpatient Clinic in Amsterdam, The Netherlands.

BACKGROUND: Increasing evidence suggests that the cervicovaginal microbiota (CVM) plays an important role in acquiring sexually transmitted infections (STIs). Here we study the CVM in a population of women notified by a sex partner for Chlamydia trachomatis infection. METHODS: We included 98 women who were contact-traced by C. trachomatis-positive sex partners at the STI outpatient clinic in Amsterdam, the Netherlands, and analyzed their cervicovaginal samples and clinical data. CVMs were characterized by sequencing the V3/V4 region of the 16S ribosomal RNA gene and by hierarchical clustering. Characteristics associating with C. trachomatis infection were examined using bivariable and multivariable logistic regression analysis. RESULTS: The CVM was characterized for 93 women, of whom 52 tested C. trachomatis positive and 41 C. trachomatis negative. We identified 3 major CVM clusters. Clustered CVM predominantly comprised either diverse anaerobic bacteria (n = 39 [42%]), Lactobacillus iners (n = 32 [34%]), or Lactobacillus crispatus (n = 22 [24%]). In multivariable analysis, we found that CVM was significantly associated with C. trachomatis infection (odds ratio [OR], 4.2 [95% confidence interval {CI}, 1.2-15.4] for women with diverse anaerobic CVM and OR, 4.4 [95% CI, 1.3-15.6], for women with L. iners-dominated CVM, compared with women with L. crispatus-dominated CVM), as was younger age (OR, 3.1 [95% CI, 1.1-8.7] for those ≤21 years old) and reporting a steady sex partner (OR, 3.6 [95% CI, 1.4-9.4]). CONCLUSIONS: Women who tested positive for Chlamydia trachomatis infection after having been contact-traced by a chlamydia-positive partner were more likely to have CVM dominated by L. iners or by diverse anaerobic bacteria, than by L. crispatus.

Low Prevalence of Urethral Lymphogranuloma Venereum Infections Among Men Who Have Sex With Men: A Prospective Observational Study, Sexually Transmitted Infection Clinic in Amsterdam, the Netherlands.

In contrast to anorectal lymphogranuloma venereum (LGV), few urogenital LGV cases are reported in men who have sex with men. Lymphogranuloma venereum was diagnosed in 0.06% (7/12,174) urine samples, and 0.9% (109/12,174) anorectal samples. Genital-anal transmission seems unlikely the only mode of transmission. Other modes like oral-anal transmission should be considered.

Design of a syndemic based intervention to facilitate care for men who have sex with men with high risk behaviour: the syn.bas.in randomized controlled trial.

BACKGROUND: Men who have sex with men (MSM) constitute a risk group for sexual transmitted infections (STIs), including HIV. Despite counselling interventions, risk behaviour remains high. Syndemic theory holds that psychosocial problems often co-occur, interact and mutually reinforce each other, thereby increasing high risk behaviours and co-occurring diseases. Therefore, if co-occurring psychosocial problems were assessed and treated simultaneously, this might decrease high risk behaviour and disease. METHOD: An open label randomized controlled trial will be conducted among 150 MSM with high risk behaviour recruited from the STI clinic of Amsterdam. Inclusion criteria are: HIV negative MSM with two STI and/or PEP treatment in the last 24 months, or HIV positive MSM with one STI in the last 24 months. All participants get questionnaires on the following syndemic domains: ADHD, depression, anxiety disorder, alexithymia and sex- and drug addiction. Participants in the control group receive standard care: STI screenings every three months and motivational interviewing based counselling. Participants in the experimental group receive standard care plus feedback based on the results of the questionnaires. All participants can be referred to co-located mental health or addiction services. The primary outcome is help seeking behaviour for mental health problems and/or drug use problems. The secondary outcomes are STI incidence and changes in sexual risk behaviour (i.e. condom use, number of anal sex partners, drug use during sex). DISCUSSION: This study will provide information on syndemic domains among MSM who show high risk behaviour and on the effect of screening and referral on help seeking behaviour and health (behaviour) outcomes. TRIAL REGISTRATION: Trial Registration at clinicaltrail.gov, identifier NCT02859935 .

Trends in antimicrobial susceptibility for azithromycin and ceftriaxone in Neisseria gonorrhoeae isolates in Amsterdam, the Netherlands, between 2012 and 2015.

Resistance of Neisseria gonorrhoeae to azithromycin and ceftriaxone has been increasing in the past years. This is of concern since the combination of these antimicrobials is recommended as the first-line treatment option in most guidelines. To analyse trends in antimicrobial resistance, we retrospectively selected all consultations with a positive N. gonorrhoeae culture at the sexually transmitted infection clinic, Amsterdam, the Netherlands, from January 2012 through September 2015. Minimum inhibitory concentrations (MICs) for azithromycin and ceftriaxone were analysed per year, and determinants associated with decreased susceptibility to azithromycin (MIC > 0.25 mg/L) or ceftriaxone (MIC > 0.032 mg/L) were assessed. Between 2012 and 2015 azithromycin resistance (MIC > 0.5 mg/L) was around 1.2%, the percentage of isolates with intermediate MICs (> 0.25 and ≤ 0.5 mg/L) increased from 3.7% in 2012, to 8.6% in 2015. Determinants associated with decreased azithromycin susceptibility were, for men who have sex with men (MSM), infections diagnosed in the year 2014, two infected sites, and HIV status (HIV; associated with less decreased susceptibility); for heterosexuals this was having ≥ 10 sex partners (in previous six months). Although no ceftriaxone resistance (MIC > 0.125 mg/L) was observed during the study period, the proportion of isolates with decreased ceftriaxone susceptibility increased from 3.6% in 2012, to 8.4% in 2015. Determinants associated with decreased ceftriaxone susceptibility were, for MSM, infections diagnosed in 2014, and pharyngeal infections; and for heterosexuals, infections diagnosed in 2014 or 2015, being of female sex, and having ≥ 10 sex partners. Continued decrease of azithromycin and ceftriaxone susceptibility will threaten future treatment of gonorrhoea. Therefore, new treatment strategies are warranted.

Leucocyte esterase dip-stick test as a point-of-care diagnostic for urogenital chlamydia in male patients: A multi-center evaluation in two STI outpatient clinics in Paramaribo and Amsterdam.

BACKGROUND: Point-of-care (POC) tests are an important strategy to address the epidemic of sexually transmitted infections (STIs). The leucocyte esterase test (LET) can be used as a POC test for chlamydia. The aim of this study was to determine the diagnostic accuracy of the LET to detect urogenital chlamydia among men at STI clinics in Paramaribo, Suriname and Amsterdam, the Netherlands. METHODS: Recruitment of patients took place in 2008-2010 in Suriname and in 2009-2010 in the Netherlands. Urine of patients was examined with the LET. The reference test was a nucleic acid amplification test (NAAT). RESULTS: We included 412 patients in Suriname and 645 in the Netherlands. Prevalence of chlamydia in Suriname and the Netherlands was respectively 22.8 and 13.6 %. The sensitivity of the LET was 92.6 % (95 % CI = 85.3-97.0) and 77.3 % (95 % CI = 67.1-85.5) respectively, the specificity was 38.1 % (95 % CI = 32.7-43.6 %) and 58.1 % (95 % CI = 53.9-62.3) respectively. The positive predictive value was 30.6 % (95 % CI = 27.3-36.4) and 22.6 % (95 % CI = 18.0-27.7) respectively and the negative predictive value was 94.5 % (95 % CI = 89.1-97.8) and 94.2 % (95 % CI = 91.1-96.4) respectively. The kappa was respectively 0.179 and 0.176. CONCLUSIONS: To diagnose urogenital chlamydia in men the LET performs poorly. It has a high negative but low positive predictive value. If the LET result is negative, chlamydia is accurately excluded, yet a positive result has a low predictive value. Whether the advantages of direct management based on LET outweigh the disadvantages of overtreatment is a subject for further studies.

Molecular assessment of bacterial vaginosis by Lactobacillus abundance and species diversity.

BACKGROUND: To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods. METHODS: Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal bacterial species was obtained from 40 females attending a Dutch sexually transmitted infection outpatient clinic, of which 20 diagnosed with BV (Nugent score 7-10), and 20 BV negative (Nugent score 0-3). RESULTS: Analysis of the bacterial communities by 16S rRNA amplicon sequencing revealed two clusters in the BV negative women, dominated by either Lactobacillus iners or Lactobacillus crispatus and three distinct clusters in the BV positive women. In the former, there was a virtually complete, negative correlation between L. crispatus and L. iners. BV positive subjects showed cluster profiles that were relatively high in bacterial species diversity and dominated by anaerobic species, including Gardnerella vaginalis, and those belonging to the Families of Lachnospiraceae and Leptotrichiaceae. Accordingly, the Gini-Simpson index of species diversity, and the relative abundance Lactobacillus species appeared consistent indicators for BV. Under the conditions used, only the 16S rRNA amplicon sequencing method was suitable to assess species diversity, while all three molecular composition profiling methods were able to indicate Lactobacillus abundance in the vaginal microbiota. CONCLUSION: An affordable and simple molecular test showing a depletion of the genus Lactobacillus in combination with an increased species diversity of vaginal microbiota could serve as an alternative and practical diagnostic method for the assessment of BV.

Cross-sectional study of genital carcinogenic HPV infections in Paramaribo, Suriname: prevalence and determinants in an ethnically diverse population of women in a pre-vaccination era.

OBJECTIVE: Cervical cancer is caused by carcinogenic human papillomavirus (HPV) infections. Prior to the introduction of HPV vaccination in Suriname, we performed a cross-sectional study to estimate the prevalence of and determinants for genital carcinogenic HPV infections. METHODS: Women were recruited at a family planning (FP) clinic and a sexually transmitted infections (STI) clinic. Vaginal swabs were used for HPV genotyping by the SPF10 PCR-DEIA-LiPA25 system. Logistic regression was used to identify determinants for carcinogenic HPV infection. RESULTS: The prevalence of any HPV was 54.2% and of carcinogenic HPV was 27.9% among 813 women attending the FP clinic. Among the 188 women attending the STI clinic, the prevalence of any HPV (76.1%) and of carcinogenic HPV (40.4%) was significantly higher. HPV52 was the most prevalent genotype in both clinics. The prevalence of HPV16 and/or 18 was 6.4% in the FP clinic and 12.2% in the STI clinic. The following determinants were independently associated with carcinogenic HPV infection among women visiting the FP clinic: ≥2 recent partners (OR 1.53; 95% CI 1.13 to 2.06), Chlamydia trachomatis co-infection (OR 1.89; 95% CI 1.32 to 2.70), disassortative ethnic sexual mixing (OR 1.50; 95% CI 1.13 to 1.99) and ethnic group (OR 1.90; 95% CI 1.27 to 2.85 for Creole and OR 1.67; 95% CI 1.06 to 2.62 for mixed ethnicity, both compared with Hindustani). No independent determinants were found among women visiting the STI clinic. CONCLUSIONS: Carcinogenic HPV is highly prevalent among women in Suriname, and not equally distributed among ethnic groups. These data provide a baseline to assess possible shifts in the prevalence of HPV genotypes following vaccination.

High performance and acceptability of self-collected rectal swabs for diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in men who have sex with men and women.

BACKGROUND: Identification of sexually transmitted infections (STI) is limited by the infrequent assessment of rectal STI. This study assesses usability of self-collected rectal swabs (SRS) in diagnosing rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: In 2006 to 2007, clients of the Amsterdam and South Limburg STI outpatient clinics reporting receptive anal intercourse were asked to fill out a questionnaire and provide SRS. A standard provider-collected rectal swab (PRS) was also taken, and both were tested for CT and NG by a nucleic acid amplification tests. SRS performance was compared with PRS as to agreement, sensitivity, and specificity. RESULTS: Prevalence of rectal CT was 11% among the 1458 MSM and 9% among the 936 women. Rectal NG prevalence was 7% and 2%. In 98% of both MSM and women, SRS and PRS yielded concordant CT test results, for NG agreement was 98% for MSM and 99.4% for women. SRS performance for CT and NG diagnosis was good in both groups and was comparable for both study regions. Slightly more (57% of MSM, 62% of women) preferred SRS to PRS or had no preference; 97% would visit the STI clinic again if SRS was standard practice. CONCLUSIONS: Because anal sex is a common practice for MSM and women, and anal STI are frequently present, rectal screening should be an essential part of an STI consultation. SRS is a feasible, valid, and acceptable alternative for MSM and women attending STI clinics, and hence should be considered for other settings as well.

Vaginal herb use and Chlamydia trachomatis infection: cross-sectional study among women of various ethnic groups in Suriname.

OBJECTIVE: Vaginal steam baths with herb leaves (herb use) is practised by some Surinamese women. We assessed herb use among women from the five most prevalent ethnic groups, and if herb use is associated with Chlamydia trachomatis infection. SETTING: Participants were recruited at a sexually transmitted infection (STI) clinic and a family planning clinic (FP) in Paramaribo, Suriname. PARTICIPANTS: 1040 women were included subsequently, comprising the following ethnic groups: Creole (26.7%), Hindustani (24.6%), Javanese (15.7%), Maroon (13.3%) and mixed descent (19.7%). METHODS: Nurses collected a questionnaire and vaginal swabs for nucleic acid amplification C. trachomatis testing. PRIMARY OUTCOMES: Determinants of vaginal herb use and C. trachomatis infection via univariable and multivariable logistic regression. RESULTS: Herb use was most common among Maroon (68.8%) and Creole women (25.2%). In multivariable analysis including only Maroon and Creole women, determinants significantly associated with vaginal herb use were (OR; 95% CI): Maroon ethnic descent (5.33; 3.26 to 8.71 vs Creole), recruitment at the STI clinic (2.04; 1.24 to 3.36 vs FP), lower education levels (3.80; 1.68 to 8.57 lower vs higher, and 2.02; 0.90 to 4.51 middle vs higher). Lower age and recruitment at the STI clinic were associated with C. trachomatis infection, but not vaginal herb use. CONCLUSION: In Suriname, vaginal herb use is common among Maroon and Creole women. Education, ethnic group and recruitment site were determinants for herb use. Vaginal herb use was not a determinant of C. trachomatis infection. Future research should focus on the effect of herb use on the vaginal microbiome and mucosal barrier.

Effect of incident hepatitis C infection on CD4+ cell count and HIV RNA trajectories based on a multinational HIV seroconversion cohort.

BACKGROUND: Most studies on hepatitis C virus (HCV)/HIV-coinfection do not account for the order and duration of these two infections. We aimed to assess the effect of incident HCV infection, and its timing relative to HIV seroconversion (HIVsc) in HIV-positive MSM on their subsequent CD4+ T-cell count and HIV RNA viral load trajectories. METHODS: We included MSM with well estimated dates of HIVsc from 17 cohorts within the CASCADE Collaboration. HCV-coinfected MSM were matched to as many HIV monoinfected MSM as possible by HIV-infection duration and combination antiretroviral therapy (cART) use. We used multilevel random-effects models stratified by cART use to assess differences in CD4+ cell count and HIV RNA viral load trajectories by HCV-coinfection status. FINDINGS: We matched 214 (ART-naive) and 147 (on cART) HCV-coinfected MSM to 5384 and 3954, respectively, matched controls. The timing of HCV seroconversion (HCVsc) relative to HIVsc had no demonstrable effect on HIV RNA viral load or CD4+ cell count trajectories. In the first 2-3 years following HCVsc CD4 cell counts were lower among HCV-coinfected MSM, but became comparable with HIV monoinfected MSM thereafter. In ART-naive MSM, during the first 2 years after HCVsc, HIV RNA viral load levels were lower or comparable with HIV monoinfected, tending to be higher thereafter. In MSM on cART, HCV had no significant effect on having a detectable HIV RNA viral load. INTERPRETATION: Irrespective of the duration of HIV infection when HCV is acquired, CD4+ cell counts were temporarily lower following HCVsc, even when on cART. The clinical implications of our findings remain to be further elucidated.

Men who have sex with men more often chose daily than event-driven use of pre-exposure prophylaxis: baseline analysis of a demonstration study in Amsterdam.

INTRODUCTION: The Amsterdam PrEP project is a prospective, open-label demonstration study at a large sexually transmitted infection (STI) clinic. We examined the uptake of PrEP; the baseline characteristics of men who have sex with men (MSM) and transgender persons initiating PrEP; their choices of daily versus event-driven PrEP and the determinants of these choices. METHODS: From August 2015 through May 2016, enrolment took place at the STI clinic of the Public Health Service of Amsterdam, the Netherlands. MSM or transgender persons were eligible if they had at least one risk factor for HIV infection within the preceding six months. Participants were offered a choice between daily or event-driven use of tenofovir/emtricitabine. Baseline data were analysed using descriptive statistics and multivariable analysis was employed to determine variables associated with daily versus event-driven PrEP. RESULTS: Online applications were submitted by 870 persons, of whom 587 were invited for a screening visit. Of them, 415 were screened for eligibility and 376 initiated PrEP. One quarter (103/376, 27%) chose event-driven PrEP. Prevalence of bacterial STI was 19.0% and mean condomless anal sex (CAS) episodes in the preceding three months were 11. In multivariable analysis, older age (≥45 vs. ≤34, aOR 2.1, 95% CI 1.2 to 3.9), being involved in a steady relationship (aOR 1.7, 95% CI 1.0 to 2.7), no other daily medication use (aOR 0.6, 95% CI 0.3 to 0.9), and fewer episodes of CAS (per log increase aOR 0.7, 95% CI 0.6 to 0.9) were determinants for choosing event-driven PrEP. DISCUSSION: PrEP programmes are becoming one of the more important intervention strategies with the goal of reducing incident HIV-infection and we were unable to accommodate many of the persons applying for this study. Offering a choice of dosing regimen to PrEP users may enable further personalization of HIV prevention strategies and enhance up-take, adherence and cost-effectiveness. CONCLUSIONS: The majority of participants preferred daily versus event-driven use. Within this majority, a high number of CAS episodes before PrEP initiation was reported and we observed a high prevalence of STI. Determinants of choosing event-driven PrEP were older age, fewer CAS episodes, no other daily medication use, and involved in a steady relationship.

HIV and hepatitis C treatment uptake among people who use drugs participating in the Amsterdam Cohort Studies, 1985-2015.

BACKGROUND: HIV-positive people who use drugs (PWUD) start antiretroviral therapy (ART) later than other risk groups, and among HCV-positive PWUD, HCV treatment uptake is low. Nowadays, HCV direct-acting antivirals (DAAs) are available and reimbursed in the Netherlands (since 2014). The Amsterdam Cohort Studies (ACS), initiated in 1985, provides us the opportunity to describe temporal trends in ART and HCV-treatment uptake among PWUD through 2015. METHODS: We analyzed data from PWUD participating in the ACS between 1985 and 2015. ART and HCV-treatment data were obtained from ACS questionnaires and medical records. Treatment uptake was defined by: treatment initiation (the proportion initiating any kind of ART/HCV treatment when treatment-naïve) and coverage (the proportion ever treated for HIV/HCV) among all HIV-/HCV-RNA-positive PWUD. Each was calculated per calendar year. We estimated the cumulative probability of ART uptake in the pre-cART (<1996) and cART era (January 1, 1996) among HIV seroconverters, with all-cause mortality as a competing risk. RESULTS: Of 1305 PWUD, 263 (20.2%) were HIV-antibody positive and 810 (62.1%) were HCV-antibody positive, at study entry. ART coverage increased over time, from 5.7% in 1990 and 42.2% in 1996 to 91.7% in 2015. The proportion initiating ART ranged from 4.8% in 1990 to 33.3% in 2011. At 8 years after HIV seroconversion, cumulative probability of ART uptake was 42.5% in the pre-cART era and 61.5% in the cART era. HCV treatment initiation peaked in 2006 (9.7%). HCV-treatment coverage was 43.9% in 2015 but lower among HIV-coinfected (23.5%) than HCV-monoinfected PWUD (52.5%). In 2015, 3.0% initiated HCV treatment with DAAs. CONCLUSION: We observed an increase in ART and HCV-treatment coverage among PWUD over time. As expected, ART uptake was higher in the cART era than the pre-cART era. Although in 2015 HCV treatment coverage was relatively high, DAA uptake was still low.

Prevalence, determinants and genetic diversity of hepatitis C virus in the multi-ethnic population living in Suriname.

Little is known about the epidemiology of HCV in Suriname, a former Dutch colony in South America. To study the prevalence, determinants and genetic diversity of HCV, a one-month survey was conducted at the only Emergency Department in the capital Paramaribo. Participants (≥18 years) completed an interviewer-led standardized HCV risk-factor questionnaire, were tested for HCV-antibodies, and if positive also for HCV RNA. The overall HCV prevalence was 1.0% (22/2128 participants; 95%CI 0.7-1.5). Male sex (OR=4.11; 95%CI 1.30-13.01), older age (OR=1.06 per year increase; 95%CI 1.04-1.09), Javanese ethnicity (OR=7.84; 95%CI 3.25-18.89) and cosmetic tattooing (OR=31.7; 95%CI 3.25-323.87) were independently associated with HCV-infection. Phylogenetic analysis revealed six distinct HCV subtypes, all HCV-genotype 2 (HCV-2): subtype 2f (also circulating in Indonesia) plus five yet unassigned HCV-2 subtypes exclusively linked to Suriname.

Treatment as prevention among injecting drug users; extrapolating from the Amsterdam cohort study.

OBJECTIVE: To determine the potential of treatment as prevention for reducing HIV incidence among injecting drug users (IDU). METHODS: Transmission dynamics of HIV as influenced by cART uptake and demographic changes were studied using an individual-based model. Parameters were based on data of the Amsterdam Cohort Study, and counterfactual treatment scenarios were examined for this city. Demography of the modeled population was also varied to allow for more general conclusions. RESULTS: We estimated that over the complete HIV epidemic among IDU in Amsterdam the historic use of cART has led to only 2% less incidence. As individuals were treated from low CD4 cell counts, their decreased infectiousness was offset by increased infectious lifetime. Large reduction in incidence could result from a test and immediate treat strategy, with elimination of HIV occurring when the average time from infection to starting treatment was less than 2 months. However, substantial proportions of new infections were prevented only if the test and treat intervention was implemented within the first few years after HIV-epidemic onset, especially for a declining IDU population. Ignoring heterogeneity in risk-behavior led to overly optimistic expectations of the prevention effects of treatment. In general, treatment led to much greater reduction in incidence compared with stopping HIV-infected IDU from lending out syringes. CONCLUSION: A test and immediate treat strategy for HIV among IDU could lead to great reductions in incidence. To fully eliminate the spread of HIV, treatment as prevention should be combined with other interventions, with behavioral intervention directed at those not yet HIV infected.

Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study.

BACKGROUND: Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status. METHODS: For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defined non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per µL or higher. We defined LTNP as non-progression during the first 10 years after seroconversion. We used longitudinal methods to characterise LTNP. FINDINGS: Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2·07 years (95% CI 1·96-2·17), giving estimated progression-free survivals of 18·4% (17·2-19·6) 5 years, 4·0% (3·6-4·5) 10 years, and 1·4% (0·9-1·5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0·28 [95%CI 0·26-0·31] per person-year at 10 years after seroconversion, 0·24 [0·19-0·29] per person-year at 15 years, and 0·18 [0·10-0·33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2·49 years [2·05-2·92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p < 0·0001) and HIV RNA load at 10 years after seroconversion (p = 0·005), but not age (p = 0·544), mode of infection (p = 0·621), sex (p = 0·676), or calendar year of seroconversion (p = 0·397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p < 0·0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p = 0·009). INTERPRETATION: Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually. FUNDING: European Union Seventh Framework Programme.

Temporal trends in mortality among people who use drugs compared with the general Dutch population differ by hepatitis C virus and HIV infection status.

OBJECTIVES: We aimed to identify temporal trends in all-cause and cause-specific mortality rates among people who use drugs (PWUD) compared with the general Dutch population and to determine whether mortality trends differed by hepatitis C virus (HCV)/HIV (co) infection status. DESIGN: Longitudinal cohort study. METHODS: Using data from the Amsterdam Cohort Studies among 1254 PWUD (1985-2012), all-cause and cause-specific standardized mortality ratios (SMRs) were calculated; SMRs were stratified by serological group (HCV/HIV-uninfected, HCV-monoinfected, and HCV/HIV-coinfected) and calendar period. Temporal trends were estimated using Poisson regression. RESULTS: The overall all-cause SMR was 13.9 (95% confidence interval 12.6-15.3). The SMR significantly declined after 1996, especially due to a decline among women (P < 0.001). The highest SMR was observed among HCV/HIV-coinfected individuals during 1990-1996 (SMR 61.9, 95% confidence interval 50.4-76.0), which significantly declined after this period among women (P = 0.001). In contrast, SMR for HCV-monoinfected, and HCV/HIV-uninfected PWUD did not significantly change over time. The SMR for non-natural deaths significantly declined (P = 0.007), whereas the SMR for HIV-related deaths was the highest during all calendar periods. CONCLUSIONS: We found evidence for declining all-cause mortality among PWUD compared with the general population rates. Those with HCV/HIV-coinfection showed the highest SMR. The decline in the SMR seems to be attributable to the decline in mortality among women. Mortality rates due to non-natural deaths came closer to those of the general population over time. However, HIV-related deaths remain an important cause of mortality among PWUD when compared with the general Dutch population. This study reinforces the importance of harm-reduction interventions and HCV/HIV treatment to reduce mortality among PWUD.

Decline in incidence of HIV and hepatitis C virus infection among injecting drug users in Amsterdam; evidence for harm reduction?

AIMS: In Amsterdam, HIV prevalence has nearly halved among injecting drug users (IDU) since 1990. Hepatitis C virus (HCV) prevalence also declined; HIV and HCV incidence dropped to nearly zero. We examined possible explanations for these time trends, among which the implementation of harm reduction measures aimed at reducing the risk behaviour of IDU. DESIGN: We used individual-based modelling of the spread of HIV and HCV. Information about demographic parameters was obtained from the Amsterdam Cohort Study (ACS) among drug users. The model included changes in inflow of new IDU and death rates over time, the latter dependent on age and time since HIV seroconversion. We considered different scenarios of risk behaviour. SETTING: IDU in Amsterdam. MEASUREMENTS: Simulated HIV and HCV incidence and prevalence were compared with ACS data. FINDINGS: Assuming that harm reduction measures had led to a strong decrease in risk behaviour over time improved the model fit (squared residuals decreased by 30%). However, substantial incidence and HIV prevalence decline were already reproduced by incorporating demographic changes into the model. In particular, lowered disease spread might be a result of depletion of high-risk IDU among those at risk for disease, and a decrease in the number of high-risk individuals in the population due to HIV-related mortality. CONCLUSIONS: Marked decreases in HIV and HCV in Amsterdam since 1990 could be due partly to harm reduction measures; however, they may also be attributable largely to changes in the IDU population. Future research aimed at quantifying the benefits of interventions should not neglect the impact of natural epidemic progression and demographic changes.

Distinct transmission networks of Chlamydia trachomatis in men who have sex with men and heterosexual adults in Amsterdam, The Netherlands.

BACKGROUND: Genovar distributions of Chlamydia trachomatis based on ompA typing differ between men who have sex with men (MSM) and heterosexuals. We investigated clonal relationships using a high resolution typing method to characterize C. trachomatis types in these two risk groups. METHODS: C. trachomatis positive samples were collected at the STI outpatient clinic in Amsterdam between 2008 and 2010 and genotyped by multilocus sequence typing. Clusters were assigned using minimum spanning trees and these were combined with epidemiological data of the hosts. RESULTS: We typed 526 C. trachomatis positive samples: 270 from MSM and 256 from heterosexuals. Eight clusters, containing 10-128 samples were identified of which 4 consisted of samples from MSM (90%-100%), with genovars D, G, J, and L2b. The other 4 clusters consisted mainly of samples from heterosexuals (87%-100%) with genovars D, E, F, I, and J. Genetic diversity was much lower in the MSM clusters than in heterosexual clusters. Significant differences in number of sexual partners and HIV-serostatus were observed for MSM-associated clusters. CONCLUSIONS: C. trachomatis transmission patterns among MSM and heterosexuals were largely distinct. We hypothesize that these differences are due to sexual host behavior, but bacterial factors may play a role as well.

Urogenital Chlamydia trachomatis infections among ethnic groups in Paramaribo, Suriname; determinants and ethnic sexual mixing patterns.

BACKGROUND: Little is known about the epidemiology of urogenital Chlamydia trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese, Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia, including the role of ethnicity, and identified transmission patterns and ethnic sexual networks among clients of two clinics in Paramaribo, Suriname. METHODS: Participants were recruited at two sites a sexually transmitted infections (STI) clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men and nurse-collected vaginal swabs were obtained for nucleic acid amplification testing. Logistic regression analysis was used to identify determinants of chlamydia. Multilocus sequence typing (MLST) was performed to genotype C. trachomatis. To identify transmission patterns and sexual networks, a minimum spanning tree was created, using full MLST profiles. Clusters in the minimum spanning tree were compared for ethnic composition. RESULTS: Between March 2008 and July 2010, 415 men and 274 women were included at the STI clinic and 819 women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age, ethnicity, and recruitment site were significantly associated with chlamydia in multivariable analysis. Participants of Creole and Javanese ethnicity were more frequently infected with urogenital chlamydia. Although sexual mixing with other ethnic groups did differ significantly per ethnicity, this mixing was not independently significantly associated with chlamydia. We typed 170 C. trachomatis-positive samples (76%) and identified three large C. trachomatis clusters. Although the proportion from various ethnic groups differed significantly between the clusters (P = 0.003), all five major ethnic groups were represented in all three clusters. CONCLUSION: Chlamydia prevalence in Suriname is high and targeted prevention measures are required. Although ethnic sexual mixing differed between ethnic groups, differences in prevalence between ethnic groups could not be explained by sexual mixing.