Nicole H. T. M. Dukers

Increase in sexually transmitted infections among homosexual men in Amsterdam in relation to HAART

Objectives: We investigated if a rise in rectal gonorrhoea and early syphilis among men who have sex with men (MSM) in Amsterdam coincided with the introduction of highly active antiretroviral therapies (HAART) in July 1996 and determined risk factors for these sexually transmitted infections (STI). Methods: Subjects were patients of the STI clinic of the municipal health service in Amsterdam. Surveillance data (1994–9) represented consultations (n=11 240) of MSM (n=6103). For analyses we used logistic regression. Results: Comparing the periods before and after the introduction of HAART, the infection rate for rectal gonorrhoea increased from 4% to 5.4% (p=.001) and for syphilis, from 0.5% to 0.8% (p = 0.050). Independent risk factors for rectal gonorrhoea (younger age, western nationality, and concurrent infection with another STI) and for early syphilis (non-western nationality and concurrent infection with rectal gonorrhoea) did not change after HAART became available. For rectal gonorrhoea, however, the infection rate increased only among men who had exclusively homosexual contacts (OR 1.38, p<0.01), compared with bisexual men. For early syphilis, the infection rate increased only among men of western nationality (OR 3.38, p<0.01) compared to men of non-western nationality. Conclusions: Infection rates of rectal gonorrhoea and early syphilis increased, indicating a change in sexual behaviour, possibly as a result of the introduction of HAART. For now, it is important to find out how sexual behaviour is changing and to keep monitoring trends in STIs (including HIV) among MSM in Amsterdam.

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma.

Background:The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposis sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposis sarcoma in HIV infection is unknown. Methods:The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposis sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposis sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus. Results:The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposis sarcoma was 3.15 (95% CI: 1.89–5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposis sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94–8.64), an additional risk of 1.60 (95% CI: 1.01–2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposis sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. Conclusions:The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposis sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposis sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.

High prevalence of syphilis and other sexually transmitted diseases among sex workers in China: potential for fast spread of HIV.

ObjectivesIn China, in the early 1980s, sexually transmitted diseases (STD) started to increase steeply. Sex workers and their clients appeared to play an important role in the spread of STD. Prostitution is illegal in China, and therefore no specific services exist for sex workers unless they are arrested and detained in re-education centres. Staff of a maternal and neonatal hospital in Guangzhou felt the need for an STD care and prevention programme for sex workers outside detention, and started a programme within their hospital, which was unique in the Chinese context. MethodsFrom March 1998 to mid-October 1999 sex workers were recruited through various outreach methods, and were interviewed, counselled and examined for the presence of STD/HIV. ResultsA total of 966 women, originating from all over China but working in Guangzhou, entered the programme. The median duration of prostitution was one year, and the median number of clients was seven per week. Antibodies to HIV were present in 1.4%. The prevalence of STD was very high: syphilis 14%, Chlamydia trachomatis 32%, gonorrhoea 8% and trichomoniasis 12.5%. Knowledge about STD/HIV transmission and condom use was poor. ConclusionGiven the high prevalence of STD, the potential for the further spread of HIV is clearly present. STD care and prevention programmes for these women, outside detention, are urgently needed, and appear also to be feasible in China.

HIV incidence on the increase among homosexual men attending an Amsterdam sexually transmitted disease clinic: using a novel approach for detecting recent infections.

ObjectiveDramatic increases have occurred in sexually transmitted diseases (STD) and in sexual risk behaviour among homosexual men in Amsterdam and internationally. We investigated whether these trends indicate a resurgence of the HIV epidemic. MethodsHIV incidence was determined among homosexual attendees of an STD clinic in Amsterdam, who had participated in semi-annual anonymous unlinked cross-sectional HIV prevalence studies from 1991 to 2001. Stored HIV-seropositive samples were tested with a less-sensitive HIV assay and, if non-reactive, were further tested for the presence of antiretroviral drugs, indicative of the use of highly active antiretroviral therapy. Seropositive men who tested non-reactive on the less-sensitive assay and had not used antiretroviral drugs were classified as recently infected (< 170 days). Annual HIV incidence and its changes were examined. ResultsAmong 3090 homosexual participants (median age 34 years), 454 were HIV infected, of whom 37 were recently infectioned. From 1991 to 2001 the overall incidence was 3.0 infections/100 person-years. Incidence increased over time (P = 0.02) and, strikingly, the increase was evident in older (⩾ 34 years) men (P < 0.01), but not in the young. Of men recently infected, 84% (n = 31) were unaware of their infection and 70.3% (n = 26) had a concurrent STD. These 26 men reportedly had sex with a total of 315 men in the preceding 6 months. ConclusionHIV incidence is increasing among homosexual attendees of an STD clinic. It is imperative to trace recently infected individuals, because they are highly infectious, and can thus play a key role in the spread of HIV.

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.

Lack of Epstein-Barr virus- and HIV-specific CD27- CD8+ T cells is associated with progression to viral disease in HIV-infection

Objective: Despite readily detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. To investigate the underlying mechanism of this loss of immune control phenotypic analysis of HIV- and Epstein–Barr virus (EBV)-specific CD8+ T cells was performed. Design: In three clinically distinct groups, long-term asymptomatics, progressors to opportunistic infections and progressors to EBV-associated non-Hodgkin lymphomas (NHL), both number and phenotype of virus-specific CD8+ T cells was studied longitudinally. Methods: The number of HIV- and EBV-specific T cells were determined using HLA-peptide tetrameric complexes. The phenotype of these virus-specific T cells was investigated by costaining with CD27 and CD45RO and thereby identifying specific subsets of CD8+ T cells. Results: Individuals co-infected with HIV and EBV persistently had low numbers of HIV-specific CD27− T cells, in contrast to rising numbers of EBV-specific CD27− CD8+ T cells. However, HIV-infected individuals developing EBV-associated AIDS-related NHL had very low numbers of EBV-specific CD27− CD8+ T cells. Higher numbers of HIV-specific CD27− CD8+ T cells were associated with delayed disease progression. Virus-specific CD27− T cells, compared with CD27+ T cells showed elevated interferon-gamma production in response to viral peptides in vitro, indicative for strong effector function. Conclusions: Taken together, our data indicate that virus-specific CD27− T cells may be important effector T cells in controlling chronic viral infections in humans and that lack of differentiation into CD27− effector T cells may lead to progression of viral disease.

Decreasing STD incidence and increasing condom use among Chinese sex workers following a short term intervention: a prospective cohort study

Objective: To describe the impact of a repeating behavioural intervention focused on preventive education and provision of STD testing and treatment services to female sex workers. Methods: A prospective cohort study of 966 sex workers (first of its kind in China) was conducted in Guangzhou from March 1998 to October 1999. At each visit information was collected on sexual behaviour, condom use and knowledge about HIV transmission and condom use, education was given, STD were diagnosed, and treatment was provided free of charge. We evaluated trends in condom use, knowledge about HIV transmission and condom use, and STD incidences. Generalised estimating equations were applied to control for repeated measurements. Results: The proportion of consistent condom use increased from the intake through the third follow up visit (from 30% to 81%), as well as the proportion of having good knowledge on HIV transmission (4.3% to 98.6%) and condom use (23.6% to 79.3%). The incidence of gonorrhoea, trichomoniasis, and chlamydia decreased over each follow up visit; from 17.5/100 person years (PY), 22.4/100PY, 65.9/100PY at the first follow up visit to 5.1/100PY, 3.0/100PY, 16.1/100PY at the third follow up visit, for each STD respectively. Conclusions: STD care and prevention programmes targeting sex workers are feasible in China and, more importantly, intervention consisting of prevention education and STD care is likely to reduce unprotected sexual behaviour and STD incidence in this group at high risk for HIV and other STD infection.

Risk factors for human herpesvirus 8 infection in a cohort of drug users in The Netherlands, 1985–1996

To elucidate the mode of human herpesvirus 8 (HHV-8) transmission in a population of Amsterdam drug users, HHV-8 seroprevalence and seroincidence were determined in 1179 drug users in the Amsterdam Cohort Studies (1985-1996). Risk factors for HHV-8 infection were examined. Serum samples were screened with an enzyme immunoassay by using HHV-8 lytic capsid (open-reading frame [ORF] 65) and latent nuclear (ORF73) antigens; positive results were confirmed by Western blot and immunofluorescence assay. Seroprevalence (men, 3.4%; women, 1.4%) and seroincidence (men, 0.08; women, 0.05/100 person-years) were low in this study. Infections with human immunodeficiency virus (HIV) type 1, hepatitis B virus (HBV), and hepatitis C virus (HCV), but not HHV-8, were associated with injection drug use (IDU). Independent risk factors for HHV-8 seropositivity were homosexual contacts and Mediterranean nationality for men and sexual contact with bisexual men, absence of a steady partner, and unprotected commercial sex for women. Unlike HIV-1, HBV, or HCV infection, HHV-8 infection is uncommon in Amsterdam drug users, as is HHV-8 transmission through IDU.

High prevalence of Epstein-Barr virus type 2 among homosexual men is caused by sexual transmission

To investigate whether Epstein-Barr virus (EBV) type 2 infection is highly prevalent among homosexual men, the prevalence of EBV type 2 was studied among homosexual and heterosexual white men who were at high and low risk for sexually transmitted diseases; these data were correlated with sexual behavior. The prevalence of EBV type 2 among homosexual men was significantly higher than it was among heterosexual men (39% vs. 6%). Among high-risk heterosexual men, prevalence was significantly higher than it was among low-risk heterosexual men (15% vs. 0). In univariate analyses, EBV type 2 infection in homosexual men was significantly associated with human immunodeficiency virus (HIV) seropositivity, increased numbers of intercourse partners, non-Dutch nationality, and human herpesvirus 8 seropositivity. In multivariate analyses, an independent association with EBV type 2 was observed only for HIV seropositivity and number of sex partners. These data support the conclusion that EBV type 2 infection is more prevalent among white homosexual men and is caused by sexual transmission.

HIV incidence and HIV testing behavior in men who have sex with men: Using three incidence sources, the Netherlands, 1984-2005

Background:In The Netherlands, the western part, including Rotterdam and Amsterdam harbors the majority of the known HIV-infected population, of whom men who have sex with men (MSM) comprise the largest transmission category. Given a general rise in sexually transmitted infections (STI) and risky sexual behavior, we examine the HIV incidence among MSM in the Netherlands with data from three different sources. Methods:To describe the HIV epidemic among MSM we use: a prospective cohort study in Rotterdam (ROHOCO: 1998–2003, n = 265) and another in Amsterdam (ACS: 1984–2005, n = 1498]) plus an anonymous HIV surveillance study (Amsterdam STI clinic: 1991–2004, n = 3733) in which HIV-positive MSM were tested with a less-sensitive HIV assay. We evaluated calendar trends in HIV incidence, also focusing on age effects. Results:Since the start of the HIV epidemic in the early 1980s, incidence has declined strongly in the ACS. In recent years, an increase was noted among older MSM attending the Amsterdam STI clinic (P = 0.0334). In both cohort studies, HIV incidence was lower and recent time-trends were not statistically significant. Among recently infected men at the STI clinic, only 40% accepted named HIV testing at their STI consultation. Conclusions:Data suggest that among MSM in the Netherlands, the HIV incidence is between one and four infections per 100 person-years. The epidemic expands among older STI clinic attendees. Prevention should be developed specifically for older men, along with a more efficient HIV testing approach such as routine HIV testing of MSM when they are screened for STI.