Ineke G. Stolte

Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic.

Background:Since 2000 outbreaks of sexually transmitted hepatitis C Virus (HCV) infections have been reported among HIV-infected men who have sex with men (MSM). We studied the prevalence and determinants of HCV-infection among MSM attending a large sexually transmitted infection (STI) clinic in the Netherlands. Methods:In 2007–2008, 3125 attendees of the STI clinic Amsterdam, including 689 MSM, participated in an anonymous biannual crosssectional survey. Participants were interviewed and screened for HIV and HCV antibodies. Additionally, all anti-HCV positive and HIV-infected individuals were tested for HCV RNA. Using phylogenetic analysis, HCV strains of the STI clinic attendees were compared with those isolated from MSM with acute HCV in 2000–2007. Determinants of HCV-infection were analysed using logistic regression. Results:Two of 532 (0.4%) HIV-negative MSM and 28 of 157 (17.8%) HIV-positive MSM were infected with HCV. Over the study period, HCV prevalence among HIV-infected MSM increased (14.6%–20.9%). Seven of 28 (25.0%) HIV/HCV coinfected MSM had acute HCV infection. Only five of 28 (17.9%) HIV/HCV coinfected MSM ever injected drugs (IDU). HIV-infection, IDU, fisting and gamma hydroxy butyrate (GHB)-use were significantly associated with HCV-infection. Phylogenetic analyses revealed a high degree of MSM-specific clustering. Conclusion:We found a high and increasing HCV prevalence in HIV-infected MSM. Though not statistically significant, this trend, and the relatively large proportion of acute infections suggest ongoing transmission of HCV in HIV-positive MSM. Regardless of IDU, rough sexual techniques and use of recreational drugs were associated with HCV-infection; phylogenetic analysis supported sexual transmission. Targeted prevention, like raising awareness and routine testing, is needed to stop the further spread among HIV-infected MSM, and to prevent possible spillover to HIV-negative MSM.

Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV Cohort Study

BACKGROUND Human immunodeficiency virus (HIV)-infected individuals may be at increased risk of age-associated noncommunicable comorbidities (AANCCs). METHODS Cross-sectional analyses of AANCC prevalence (including cardiovascular, metabolic, pulmonary, renal, bone, and malignant disease) and risk factors in a prospective cohort study of HIV type 1-infected individuals and HIV-uninfected controls, who were aged ≥45 years and comparable regarding most lifestyle and demographic factors. RESULTS HIV-infected participants (n = 540) had a significantly higher mean number of AANCCs than controls (n = 524) (1.3 [SD, 1.14] vs 1.0 [SD, 0.95]; P < .001), with significantly more HIV-infected participants having ≥1 AANCC (69.4% vs 61.8%; P = .009). Hypertension, myocardial infarction, peripheral arterial disease, and impaired renal function were significantly more prevalent among HIV-infected participants. Risk of AANCC by ordinal logistic regression was independently associated with age, smoking, positive family history for cardiovascular/metabolic disease, and higher waist-to-hip ratio, but also with HIV infection (odds ratio, 1.58 [95% confidence interval, 1.23-2.03]; P < .001). In those with HIV, longer exposure to CD4 counts <200 cells/µL, and, to a lesser extent, higher levels of high-sensitivity C-reactive protein and soluble CD14, and longer prior use of high-dose ritonavir (≥400 mg/24 hours) were each also associated with a higher risk of AANCCs. CONCLUSIONS All AANCCs were numerically more prevalent, with peripheral arterial, cardiovascular disease, and impaired renal function significantly so, among HIV-infected participants compared with HIV-uninfected controls. Besides recognized cardiovascular risk factors, HIV infection and longer time spent with severe immunodeficiency increased the risk of a higher composite AANCC burden. There was a less pronounced contribution from residual inflammation, immune activation, and prior high-dose ritonavir use.

Ongoing HIV-1 transmission among men who have sex with men in Amsterdam: a 25-year prospective cohort study

Background:To examine the suggested resurgence of the HIV epidemic among men who have sex with men (MSM), we studied trends in HIV-1 incidence rates, sexual risk behaviour, risk factors for HIV-1 seroconversion, and source of HIV-1 infection among MSM in the Amsterdam Cohort Studies from 1984 to 2009. Methods:Trends in HIV-1 incidence and risk factors for HIV-1 infection were studied using Poisson regression. Trends in sexual risk behaviour were evaluated using logistic regression, correcting for intra-individual correlation via generalized estimating equations. Trends in the source of HIV-1 infection were modelled via logistic regression. Results:Of 1642 HIV-1-negative individuals, 217 seroconverted during follow-up. HIV-1 incidence rates strongly decreased from 8.6/100 person-years in 1985 to 1.3/100 person-years in 1992; remained relatively stable around 1.0/100 person-years between 1992 and 1996, and slowly increased to 2.0/100 person-years in 2009 (P = 0.14; linear trend 1996–2009). Reports of unprotected anal intercourse (UAI) increased significantly from 1996 onwards. HIV-1 seroconversion was associated with receptive UAI with casual partners, more than five sexual partners, a history of gonorrhoea (all in the preceding 6 months), and a lower educational level. Currently, MSM are more likely to have contracted HIV-1 from casual partners than from steady partners, but trends of recent years suggest that steady partners became a growing source with increasing age. Conclusions:Following increases in sexual risk behaviour from 1996 onwards, HIV-1 continues to spread among MSM. Targeted prevention messages should continue to focus on sexual behaviour with casual partners, but also on sexual behaviour within steady relationships.

Perceived viral load, but not actual HIV-1-RNA load, is associated with sexual risk behaviour among HIV-infected homosexual men.

Background: Increases in sexual risk behaviour and sexually transmitted infections among HIV-infected homosexual men after the introduction of highly active antiretroviral therapy (HAART) confirm the need for innovative prevention activities. The present study focused on time trends in sexual risk behaviour and predictors for unprotected anal intercourse in the HAART era among HIV-infected homosexual men. Methods: In 2000–2003, 57 HIV-infected homosexual men (mean age 45 years) were interviewed in three serial data waves. Logistic regression, correcting for repeated measurements, was used to assess time trends in risky sex, and the association between HAART-related beliefs, and both the perceived and actual viral load level and CD4 cell counts and subsequent risky sex. Results: Risky sex with casual partners increased from 10.5% in 2000 to 27.8% in 2003 (P < 0.01), and with steady partners of negative or unknown HIV status from 5.3% to 10.7% (P = 0.6). Homosexual men with a favourable perception of their viral load were more likely to engage in subsequent risky sex with steady partners of negative or unknown HIV status than men with a less favourable perception of their viral load; this association was independent of the actual HIV-1-RNA load and CD4 cell counts. Conclusion: Risky sex increased in this group of HIV-infected homosexual men. The perceived viral load, but not the actual load, is associated with subsequent risky sex with steady partners of negative or unknown HIV status. Care givers should discuss with patients not only their actual viral load and CD4 cell count but also their perceived viral load.

Anal and penile high-risk human papillomavirus prevalence in HIV-negative and HIV-infected MSM.

Objective:Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM. Design:Analysis of baseline data from a prospective cohort study. Methods:MSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Participants completed risk-factor questionnaires. HPV DNA was analyzed in anal and penile shaft self-swabs and genotyped using a sensitive PCR and reverse line blot assay (SPF10-PCR-DEIA-LiPA25-system). Multivariable logistic regression analyses were performed to assess determinants of high-risk HPV infection. Results:MSM (n = 778) were recruited in 2010–2011, of whom 317 (41%) were HIV-infected. Prevalence of anal high-risk HPV infection was 45% in HIV-negative versus 65% in HIV-infected MSM (P <0.001). HPV-16 was the most frequently detected type and was more common in HIV-infected MSM (13% in HIV-negative and 22% in HIV-infected MSM; P = 0.001). Prevalence of penile high-risk HPV infection was 16% in HIV-negative and 32% in HIV-infected MSM (P <0.001). In multivariable analyses, HIV infection remained associated with anal [adjusted odds ratio (aOR) 2.2; 1.8–2.7] and penile (aOR 2.0; 1.4–2.9) high-risk HPV infection. Higher number of lifetime male sex partners was significantly associated with anal and penile high-risk HPV in HIV-negative, but not HIV-infected MSM. Receptive anal intercourse was associated with anal high-risk HPV in HIV-infected MSM. Conclusion:Anal and penile high-risk HPV infections are very common in MSM. HIV infection is a strong and independent determinant for anal and penile high-risk HPV infection. Determinants for HPV infection appear to differ between HIV-negative and HIV-infected MSM.

Serosorting and sexual risk behaviour according to different casual partnership types among MSM: the study of one-night stands and sex buddies

Among HIV-negative men who have sex with men (MSM), any incident of unprotected anal intercourse (UAI) between casual partners is usually regarded as risky for HIV transmission. However, men are increasingly using knowledge of their casual partners HIV-status to reduce HIV risk during UAI (i.e., serosorting). Since familiarity between casual partners may lead to higher levels of UAI and serosorting, we examined how often men have UAI and practice serosorting with three types of casual partnerships that differ in their degree of familiarity. We included 240 HIV-negative men of the Amsterdam Cohort Study among MSM. We distinguished three types of casual partnerships: one-night stand (“met by chance and had sex only once”); multiple-time casual partner (“met and had sex with several times”) and the “regular” casual partner (“sex buddy”). Serosorting was defined as UAI with an HIV-concordant partner. Generalised estimating equations analyses were used to examine the association between type of casual partnership and sexual risk behaviour. Analyses revealed that men with a sex buddy were more likely to have UAI than men with a one-night stand (OR [95%CI] 2.39 [1.39–4.09]). However, men with a sex buddy were also more likely to practice serosorting than men with a one-night stand (OR [95%CI] 5.20 [1.20–22.52]). Men with a sex buddy had more UAI but also reported more serosorting than men with a one-night stand. As a result, the proportion of UAI without serosorting is lower for men with a sex buddy, and therefore men might have less UAI at risk for HIV with this partner type. However, the protective value of serosorting with a sex buddy against HIV transmission needs to be further established. At this time, we suggest that a distinction between the one-night stand and the sex buddy should be incorporated in future studies as men behave significantly different with the two partner types.

Less decrease in risk behaviour from pre-HIV to post-HIV seroconversion among MSM in the combination antiretroviral therapy era compared with the pre-combination antiretroviral therapy era.

Objective:To gain insight in the ongoing HIV transmission, we compared sexual risk behaviour pre-HIV and post-HIV seroconversion in 206 MSM participating in the Amsterdam Cohort Studies (1984–2008) before and after the introduction of combination antiretroviral therapy (cART). Design and methods:MSM completed behavioural questionnaires and were tested for HIV antibodies every 6 months. Trends in anal intercourse and number of sex partners from 4 years before HIV seroconversion until 4 years after diagnosis were analysed with latent class random effects logistic regression models. Results:The risk of having unprotected anal intercourse (UAI) 1 year after HIV diagnosis decreased significantly when compared with 1 year before diagnosis in both the pre-cART era [difference, 30%; 95% confidence interval (CI), 22–36%] and cART era (difference, 19%; 95% CI, 9–30%). In contrast to a continuing decrease of UAI in the pre-cART era, the probability of UAI in the cART era increased again to preseroconversion levels (61%; 95% CI, 48–74%)) 4 years after diagnosis. Conclusion:This study provides evidence that recently seroconverted MSM reduce their sexual risk behaviour following HIV diagnosis both in the pre-cART as well as the cART period. However, in the cART period this reduction in sexual risk behaviour is less and returns to pre-cART levels within 4 years. These findings not only confirm the need for early HIV testing but also make it clear that much more effort should go into identifying, counselling, and possibly treating recently seroconverted MSM who have been found to be one of the most important drivers of HIV transmission among MSM.

Long-term follow-up: no effect of therapeutic vaccination with HIV-1 p17/p24:Ty virus-like particles on HIV-1 disease progression

Long-term effects of therapeutic vaccination of human immunodeficiency virus (HIV)-1-infected subjects with HIV-1 p17/p24:Ty virus-like particles (p24-VLP) on progression to AIDS, death, a CD4 cell count <or=200 cells/mm(3) and CD4 cell count decline were studied in a multicenter cohort study of 56 individuals who participated in a phase II double-blind placebo-controlled trial with p24-VLP in 1993. Using Cox proportional hazard analysis, no difference between vaccine and placebo groups was found in progression to death (adjusted hazard rate (HR): 0.68 (95% CI: 0.05-7.83), AIDS (adjusted HR: 1.07 (95% CI: 0.21-5.36)) and a CD4 cell count <or=200 cells/mm(3) (adjusted HR: 1.00 (95% CI: 0.35-2.87)). Using linear regression with correction for multiple visits within one person, no effect of vaccination on CD4 cell count decline, adjusted for antiretroviral therapy (ART) use, was found (P=0.98). In conclusion, therapeutic vaccination with p24-VLP is not related to slower HIV-1 disease progression.

Stabilizing incidence of hepatitis C virus infection among men who have sex with men in Amsterdam.

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Low Bone Mineral Density in Patients With Well-Suppressed HIV Infection: Association With Body Weight, Smoking, and Prior Advanced HIV Disease

BACKGROUND Human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) may both contribute to the higher prevalence of osteoporosis and osteopenia in HIV-infected individuals. METHODS Using dual-energy X-ray absorptiometry, we compared lumbar spine, total hip, and femoral neck bone mineral density (BMD) in 581 HIV-positive (94.7% receiving cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged ≥45 years. We used multivariable linear regression to investigate independent associations between HIV, HIV disease characteristics, ART, and BMD. RESULTS The study population largely consisted of men who have sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV infection (13.3% vs 6.7%; P<.001). After adjustment for body weight and smoking, being HIV-positive was no longer independently associated with BMD. Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a Centers for Disease Control and Prevention class B or C event. Interestingly, regardless of HIV status, younger MSM had significantly lower BMD than older MSM, heterosexual men, and women. CONCLUSIONS The observed lower BMD in treated HIV-positive individuals was largely explained by both lower body weight and more smoking. Having experienced symptomatic HIV disease, often associated with weight loss, was another risk factor. The low BMD observed in younger MSM remains unexplained and needs further study.