Maria Prins

Major decline of hepatitis C virus incidence rate over two decades in a cohort of drug users

Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20-year period (1985–005), the authors evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever-injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level.

The HIV RNA setpoint theory revisited

BackgroundThe evolution of plasma viral load after HIV infection has been described as reaching a setpoint, only to start rising again shortly before AIDS diagnosis. In contrast, CD4 T-cell count is considered to show a stable decrease. However, characteristics of marker evolution over time depend on the scale that is used to visualize trends. In reconsidering the setpoint theory for HIV RNA, we analyzed the evolution of CD4 T-cell count and HIV-1 RNA level from HIV seroconversion to AIDS diagnosis. Follow-up data were used from two cohort studies among homosexual men (N = 400), restricting to the period before highly active antiretroviral therapy became widely available (1984 until 1996). Individual trajectories of both markers were fitted and averaged, both from seroconversion onwards and in the four years preceding AIDS diagnosis, using a bivariate random effects model. Both markers were evaluated on a scale that is directly related to AIDS risk.ResultsIndividuals with faster AIDS progression had higher HIV RNA level six months after seroconversion. For CD4 T-cell count, this ordering was less clearly present. However, HIV RNA level and CD4 T-cell count showed qualitatively similar evolution over time after seroconversion, also when stratified by rate of progression to AIDS. In the four years preceding AIDS diagnosis, a non-significant change in HIV RNA increase was seen, whereas a significant biphasic pattern was present for CD4 T-cell decline.ConclusionHIV RNA level has more setpoint behaviour than CD4 T-cell count as far as the level shortly after seroconversion is concerned. However, with respect to the, clinically more relevant, marker evolution over time after seroconversion, a setpoint theory holds as much for CD4 T-cell count as for HIV RNA level.

Hepatitis C virus prevalence in The Netherlands: migrants account for most infections

A population-based anti-hepatitis C virus (HCV) prevalence is important for surveillance purposes and it provides insight into the burden of disease. The outcomes of recent studies in the general Dutch population as well as recent HCV data from specific risk groups including migrants, men who have sex with men (MSM) and injecting drug users (IDUs), were implemented in a modified version of the Workbook Method (a spreadsheet originally designed for HIV estimations), to estimate Dutch HCV seroprevalence. The estimated national seroprevalence of HCV was 0·22% (min 0·07%, max 0·37%), corresponding to 28 100 (min n = 9600, max n = 48 000) HCV-infected individuals in The Netherlands. Of these, first-generation migrants from HCV-endemic countries (HCV prevalence ≥2%) accounted for the largest HCV-infected group, followed by IDUs and HIV-positive MSM.

Undetectable Viral Load and the Decision to Engage in Unprotected Anal Intercourse Among HIV-Positive MSM

We investigated how often HIV-positive MSM (nxa0=xa0177) decide to engage in unprotected anal intercourse (UAI) because they have an undetectable viral load (UVL). We found that 20–57xa0% of the UAI acts were related to having UVL, varying by partner type and partner HIV status. Among HIV-concordant partners, consideration of UVL before engaging in UAI was more prevalent with sex buddies (55xa0%) than with casual partners (20xa0%), although marginally significant (pxa0=xa00.051). Among HIV-discordant partners, no significant difference was found in the frequency of UVL considerations before engaging in UAI: 40xa0% with sex buddies versus 57xa0% with casual partners. Interestingly, while the decision to engage in UAI based on UVL was frequently discussed with HIV-concordant partners (>91xa0%), it was only discussed with HIV-discordant partners in 13–25xa0% of the UAI cases (according to partner type), suggesting that the decision was mostly unilateral.

HCV-specific T-cell responses in injecting drug users : evidence for previous exposure to HCV and a role for CD4+ T cells focussing on nonstructural proteins in viral clearance

Summary.u2002 In order to understand the parameters associated with resolved hepatitis C virus (HCV)‐infection, we analysed the HCV‐specific T‐cell responses longitudinally in 13 injecting drug‐users (IDUs) with a prospectively identified acute HCV infection. Seven IDUs cleared HCV and six IDUs remained chronically infected. T‐cell responses were followed in the period needed to resolve and a comparable time span in chronic carriers. Ex vivo T‐cell responses were measured using interferon‐γ Elispot assays after stimulation with overlapping peptide pools spanning the complete HCV genome. CD4+ memory‐T‐cell responses were determined after 12‐day stimulation with HCV proteins. The maximum response was compared between individuals. The T‐cell responses measured directly ex vivo were weak but significantly higher in resolvers compared to chronic carriers, whereas the CD4+ memory‐T‐cell response was not different between resolvers and chronic carriers. However, HCV Core protein was targeted more often in chronic carriers compared to individuals resolving HCV infection. CD4+ T‐cell responses predominantly targeting nonstructural proteins were associated with resolved HCV infection. Interestingly, observation of memory‐T‐cell responses present before the documented HCV‐seroconversion suggests that reinfections in IDUs occur often. The presence of these responses however, were not predictive for the outcome of infection. However, a transition of the HCV‐specific CD4+ memory‐T‐cell response from targeting Core to targeting nonstructural proteins during onset of infection was associated with a favourable outcome. Therefore, the specificity of the CD4+ memory‐T‐cell responses measured after 12‐day expansion seems most predictive of resolved infection.

Repeated STI and HIV testing among HIV-negative men who have sex with men attending a large STI clinic in Amsterdam: a longitudinal study

Objective In the Netherlands, men who have sex with men (MSM) are advised via informal guidelines to test for STI at least annually. We estimated the proportion of HIV-negative MSM testing repeatedly at 12-month or smaller intervals at a large STI clinic in the Netherlands. In addition, we explored whether repeated testing is related to risk behaviour. Design and methods Longitudinal data of HIV-negative MSM visiting the Amsterdam STI clinic between 2009 and 2012 were analysed. To estimate the timing of repeated testing, Kaplan–Meier methods were used. Determinants for repeated testing (distinguishing testing at 12-month or smaller intervals and less than 12-monthly testing, with single testers as reference group) were identified using multivariate multinomial logistic regression analyses. Results In total, 19u2005479 consultations of 9174 HIV-negative MSM were identified. Of these MSM, 35% (95% CI 33% to 36%) were estimated to return to the STI clinic within 1u2005year following baseline consultation. Among 1767 men with at least two consultations and at least 2u2005years between baseline and last consultation, 43% tested repeatedly at 12-month or smaller intervals in those first 2u2005years. Repeated testers reported higher sexual risk behaviour (ie, only casual or both casual and steady sex partners, higher numbers of sex partners) at baseline compared with single testers. This effect tended to be slightly stronger for men testing repeatedly at 12-month or smaller intervals. Conclusions The proportion of MSM testing for STI annually is low. MSM testing repeatedly had higher baseline levels of risk behaviour. Strategies to motivate MSM to test annually should be explored.

Vaginal high-risk human papillomavirus infection in a cross-sectional study among women of six different ethnicities in Amsterdam, the Netherlands: the HELIUS study

Objective In the Netherlands the incidence of cervical cancer is higher among ethnic minority populations compared with the general Dutch population. We investigated the prevalence of, and risk factors associated with, vaginal high-risk human papillomavirus (hrHPV) infection in women of six different ethnicities living in Amsterdam. Methods For this cross-sectional study we selected women aged 18–34u2005years old of six ethnicities from the large-scale multiethnic HEalthy LIfe in an Urban Setting study. Self-collected vaginal swabs were tested for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay (short PCR fragment (SPF)10-PCR DNA enzyme immunoassay/LiPA25-system version-1, delft diagnostic laboratory (DDL)). Participants completed a questionnaire regarding demographics and sexual behaviour. Logistic regression using generalised estimating equations was used to assess risk factors of hrHPV, and to investigate whether prevalence of hrHPV differed among ethnicities. Results The study population consisted of 592 women with a median age of 27 (IQR: 23–31) years. Dutch and African Surinamese women reported the highest sexual risk behaviour. HrHPV prevalence was highest in the Dutch (40%) followed by the African Surinamese (32%), Turkish (29%), Ghanaian (26%), Moroccan (26%) and South-Asian Surinamese (18%). When correcting for sexual risk behaviour, the odds to be hrHPV-positive were similar for all non-Dutch groups when compared with that of the Dutch group. Conclusions We found an overall higher hrHPV prevalence and higher sexual risk behaviour in the native Dutch population. Further research is needed to unravel the complex problem concerning cervical cancer disparities, such as differences in participation in the cervical cancer screening programme, or differences in clearance and persistence of hrHPV.

High-risk human papillomavirus seroprevalence in men and women of six different ethnicities in Amsterdam, the Netherlands: The HELIUS study

Background Ethnic variations in the (sero)prevalence of Human Papillomavirus (HPV) and HPV related diseases have been observed previously. We explored if high-risk HPV (hrHPV) seropositivity indeed differs among 6 ethnic groups in Amsterdam the Netherlands and assessed if hrHPV seroprevalence is higher among women than men within each ethnic group, both after adjustment for confounders. Methods From the multi-ethnic HEalthy Life In an Urban Setting (HELIUS) study in Amsterdam (the Netherlands) we randomly selected 4637 men and women aged 18–44 years with a Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, or Turkish ethnicity. Blood samples were tested for HPV-16,−18,−31,−33,−45,−52, and −58 antibodies using a validated Luminex-based multiplex serology assay. We assessed the association of both ethnicity and gender with hrHPV seropositivity using logistic regression models with generalised estimating equations. Results The hrHPV seroprevalence in Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan, and Turkish participants was 18%, 12%, 23%, 19%, 17%, and 15% in men, and 30%, 22%, 34%, 31%, 14%, and 15% in women, respectively. HrHPV seroprevalence of non-Dutch men did not differ significantly from Dutch men. HrHPV seroprevalence was significantly higher among African Surinamese women, and significantly lower among Moroccan and Turkish women when compared to Dutch women. These differences were not significant anymore after adjustment for demographic, health, and sexual behavioural differences between ethnicities. HrHPV seroprevalence varied by age, age of sexual debut, and lifetime sexual partners among women but not among men. Seroprevalence of hrHPV was higher among women than among men, except in the Turkish group. Conclusion Among women hrHPV seroprevalence differed by ethnicity, yet among men no pronounced differences were observed across ethnicities.

Prevalence and determinants of insufficient work ability in older HIV-positive and HIV-negative workers.

PurposeTo explore whether the prevalence and determinants of insufficient work ability (WA) of older HIV-positive workers differ from a comparable group of HIV-negative workers.MethodsCross-sectional data from 359 HIV-negative and 264 HIV-positive middle-aged individuals (45–65xa0years) participating in paid labor, collected within the AGEhIV Cohort Study between October 2010–September 2012, were selected. Data were collected by self-administered questionnaires and physical examination. Participants self-rated their current WA, ranging from 0 to 10. WA was dichotomized into insufficient (<6) and sufficient (≥6). Using univariable and multivariable logistic regression, we studied the independent effect of HIV status on insufficient WA and determinants of insufficient WA.ResultsOverall, 8xa0% of participants reported insufficient WA (HIV-positive 9 vs. HIV-negative 7xa0%, Pxa0=xa00.20). Twice as many HIV-positive as HIV-negative individuals were declared partly unfit for work (6 vs. 3xa0%, Pxa0=xa00.02). HIV status itself was not associated with WA in univariable and multivariable analyses. Multivariable analyses revealed that low educational level, working fewer hours, being partly unfit for work, experiencing a high need for recovery after work, staying home from work ≥2 times in the past 6xa0months, and reporting depressive symptoms were associated with insufficient WA, independent of HIV status.ConclusionsHIV-positive individuals aged 45–65xa0years participating in paid labor seem to function as well at work as HIV-negative individuals. HIV-positive participants were more often formally declared partly unfit for work, but percentages were low in both groups. Knowledge of determinants of insufficient WA may help employers and professionals to optimize WA.

P1-S2.74 How patterns of migration may influence heterosexual HIV transmission

Background Ethnic minorities originating from countries with high HIV prevalence account for a large number of heterosexually acquired HIV infections in Western European countries. These groups may be infected before migrating and they may engage in unsafe sexual practices both in the country of residence and in their country of origin. We investigate how patterns of migration may affect the heterosexual HIV epidemic in the Netherlands. Methods A mathematical model was used that describes the transmission of HIV infection in heterosexual partnerships between African migrants, Caribbean migrants, and the local Dutch population. Acquiring HIV infection before migrating to the Netherlands or during trips to the country of origin was also accounted for in the model. Results The estimated HIV incidence among adult heterosexuals in 2010 was 1.50 new infections per 100u2008000 individuals per year. If the number of migrants entering the country increases, then the incidence of HIV will increase, although the change among the local Dutch will be negligible. Moreover, if HIV prevalence among those migrating to the Netherlands (at the time of entry to the country) is higher, then the incidence in the respective ethnic groups will increase; among the other ethnic groups, the increase will be very small. Conclusions Changes in patterns of migration can have a considerable impact on HIV transmission within ethnic minority communities in the Netherlands, but they hardly have any impact on transmission in the local population. Therefore, limiting migration and introducing travel restrictions would likely have no effect on HIV incidence in countries with low HIV prevalence among heterosexuals. Policy making should focus on targeted interventions, to reduce the burden of HIV disease in migrant communities.