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Biomedical subjects

A van den Hoek

Publications and source records attributed to A van den Hoek.

At least 19 recordsLinked to original sources

Determinants of high-risk sexual behavior among immigrant groups in Amsterdam: implications for interventions.

OBJECTIVES: To determine predictors for sexual risk behavior among immigrant men in Amsterdam. METHODS: From May 1997 to July 1998, 650 men from Surinam, the Antilles, and Ghana were recruited by convenience sampling. Multivariate logistic regression was used to find independent predictors for 1) multiple sex partners (>sexual 1 partner in the past year), 2) unprotected sex with casual partners in The Netherlands, 3) sexual activity in country of origin, and 4) unprotected sex in country of origin. RESULTS: 1) Multiple sex partners were reported by 50% of respondents. Independent predictors were a recent infection with a sexually transmitted disease (STD), youth, low educational level, Afro-Surinamese origin, lack of a long-term relationship and history of commercial sex contact. 2) Unprotected sex occurred in 24% of casual partnerships. Independent predictors were a recent STD infection, low educational level, use of hard drugs, age between 20 and 29, few sexual partners, unprotected sex in country of origin, and a partner from the respondent's ethnic group. 3) During the past 5 years, 24% were sexually active in country of origin. Independent predictors were Ghanaian origin, age over 20, a relatively high income, and multiple partners. 4) Unprotected sex occurred in 39% of the partnerships in country of origin. Independent predictors were low educational level, history of STDs, lack of health insurance, Ghanaian origin, frequent visits to home country, few sexual partners, and unprotected sex with casual partners in The Netherlands. CONCLUSION: Among immigrant men in Holland, important target groups for AIDS prevention programs have been identified. Men who visit their country of origin should be made aware of the risk of sexual contact with local women. Furthermore, it should be taken into account that immigrant men use condoms less frequently with women of their own ethnic group than with Dutch women.

Adolescent↗

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

OBJECTIVES: In 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. METHODS: From 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. RESULTS: A 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. CONCLUSION: Given 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.

Adult↗

Comparative model-based analysis of screening programs for Chlamydia trachomatis infections.

The design of a screening program for asymptomatic genital infections with Chlamydia trachomatis, requires decisions about which sex or age group should be targeted and whether partner referral should be included in the program. To investigate the effects of various screening programs on the prevalence and incidence of asymptomatic C. trachomatis infections in women, in May 1996 to April 1997 in Bilthoven, the Netherlands, the authors used a stochastic simulation model for C. trachomatis transmission in an age-structured, heterosexual population with a sexually highly active core group. Different screening scenarios were implemented over a time period of 10 years. Prevalence, incidence, and the fraction of infected persons found by partner referral were computed. Through screening of men and women between ages 15 and 24 years (baseline scenario), the prevalence of asymptomatic infections in women could be reduced from 4.2% to 1.4% in 10 years. Increasing the age range of screening up to ages 29 or 34 years led to prevalences of 0.4% and 0.06%, respectively, after 10 years. About 28% of all infected persons were found via partner referral. There are considerable indirect positive effects of screening on those population groups that are not included in the screening because of the reduced risk of becoming infected. Partner referral contributes substantially to prevalence reduction.

Adolescent↗

Pregnancies before and after HIV diagnosis in a european cohort of HIV-infected women. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: Because most HIV-infected women are of reproductive age, we investigated whether their reproduction planning was affected by their HIV diagnosis. DESIGN: The European women study is a prospective, multicentre cohort of 485 HIV-infected women with a known interval of seroconversion. METHODS: The incidence of pregnancy was measured with person-time methods. Generalized estimating equation analysis was used to determine risk factors for pregnancy and pregnancy outcomes. RESULTS: In 449 women, the age-adjusted incidence of pregnancies decreased from 8.6 before HIV diagnosis to 8.2 and 6.0 per 100 person-years in 0-4 and over 4 years after HIV diagnosis, respectively (P = 0.14). The proportion of induced abortions increased from 42% before to 53% after HIV diagnosis (P < 0.05). The risk of spontaneous abortion did not increase as a result of HIV infection. Since 1995, the proportion of births increased (P = 0.009), whereas that of induced abortions decreased (P = 0.01) compared with earlier years. An increased risk of pregnancy after HIV diagnosis was found in northern and central European women compared with southern European women; there was a lower risk in single women than in women with a steady partner. Of all pregnant women, single women, women between 15 and 25 years of age, and women with multiple partners were at increased risk for induced abortion both before and after HIV diagnosis. CONCLUSION: The incidence of pregnancy decreased with HIV disease progression. Pregnancies after HIV diagnosis appear to be related largely to social and cultural attitudes. The number of induced abortions was high before HIV diagnosis and it significantly increases thereafter.

Abortion, Induced↗

Regional differences in HIV testing among European patients with sexually transmitted diseases: trends in the history of HIV testing and knowledge of current serostatus.

OBJECTIVES: To determine trends in (1) HIV testing and knowledge of current serostatus and (2) clinic-visits of aware HIV-infected patients and (3) to determine associates of incident HIV infection among patients with sexually transmitted disease (STD) in 15 countries participating in a European Community anonymous HIV seroprevalence survey. METHODS: Demographics, STD diagnosis, self-reported history of HIV tests and current HIV test results were collected for patients diagnosed with one of 12 pre-selected STDs. Incident HIV infections were determined among patients who reported prior HIV-negative test results. RESULTS: Between June 1990 and December 1996, 66560 STD patients were tested for HIV. Of these, 1581 (2.4%) reported a prior HIV-positive test. Of 41727 (62%) patients who reported no previous HIV test, 611 (1.4%) were HIV infected. Of 20785 (31%) patients who reported a prior HIV-negative test, 213 (1.0%) were HIV infected. Of 2467 (4%) patients without prior HIV test data available 123 (4.9%) were HIV infected. Overall, 63% of HIV-seropositive patients was aware of their HIV infection. Over time, the proportion of aware HIV-seropositive patients increased in some exposure categories in south and central Europe. Among the 11684 patients who reported dates of prior HIV-negative tests, 108 HIV infections were found. Compared with the north, HIV incidence was higher in the central region [odds ratio (OR), 1.23; 95% confidence interval (CI), 0.71-2.12] and in the south (OR, 4,39; 95% CI, 2.80-6.88) in all exposure categories except homosexual men. CONCLUSIONS: Two-thirds of patients with an STD had never been tested for HIV. Of all HIV infections found, 32% were undiagnosed, indicating missed opportunities for counselling, safe sex education and referral for treatment. HIV testing should be routinely offered to all STD patients.

AIDS Serodiagnosis↗

Cervical squamous intraepithelial lesions in HIV-infected women: prevalence, incidence and regression. European Study Group on Natural History of HIV Infection in Women.

OBJECTIVES: To assess the impact of HIV-related immunodeficiency and antiretroviral treatment on the occurrence and evolution of abnormal Papanicolaou tests. STUDY DESIGN: Cohort of 485 HIV-infected women with a known date of infection, enrolled during May 1993-April 1998 in 23 centres (gynaecology, infectious disease or STD clinics, or drug treatment centres) in 12 European countries; in 21 centres, follow-up was performed every 6 months (median follow-up: 2 years). METHODS: Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. The prevalence of squamous intraepithelial lesions (SIL), the incidence of SIL and regression from low-grade SIL were studied according to CD4 count after controlling for HPV detection results. RESULTS: Compared with women with CD4 cell counts > 500 x 10(6)/l, women with CD4 cell counts < 200 x 10(6)/l had a twofold increase in both prevalence and incidence of SIL and in non-regression from untreated low-grade SIL; in addition, these women had a lower response rate to treatment of high-grade cervical intraepithelial neoplasia. The increase in SIL incidence associated with a low CD4 cell count was significant in women not receiving antiretroviral treatment (relative risk, CD4 cell count 200-499 x 10(6)/l, 1.9; CD4 cell count < 200 x 10(6)/l, 2.9; CD4 cell count > 500 x 10(6)/l, reference), whereas it was less marked and not statistically significant in treated women. CONCLUSIONS: Severe HIV-related immunodeficiency strongly increases the risk of occurrence of SIL; antiretroviral treatment may reduce this risk, probably by restoring or at least preserving immune function.

Adolescent↗

Sexually transmitted infections in European HIV-infected women: incidence in relation to time from infection. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: To investigate the prevalence and incidence of sexually transmitted infections (STI) in HIV-infected women in relation to time from infection and sexual behaviour. DESIGN: The European study on the natural history of HIV infection in women is a prospective cohort study of 487 HIV-infected women with a known interval of seroconversion from 12 European countries. METHODS: Incidence was measured with person-time methods. Generalized estimating equations analysis was used to determine risk factors for STI. RESULTS: At entry, 15% of the women were diagnosed with at least one acute STI (chlamydial infection, trichomoniasis or gonorrhoea), 10% with at least one other STI (genital warts or genital ulcerations) and 13% with vaginal candidiasis. Although frequently diagnosed during follow-up, the occurrence of acute STI and vaginal candidiasis decreased, whereas the occurrence of other STI increased with ongoing time from HIV infection. Furthermore, women with a history of prostitution [relative risk (RR), 2.00; 95% confidence interval (95% CI), 1.20-3.33] and women with irregular condom use (RR, 7.74; 95% CI, 3.52-17.0) were at higher risk for an acute STI. CONCLUSIONS: Although STI diagnoses were frequent, the occurrence of acute STI declined with time from infection which might be explained by changed sexual behaviour over time. The occurrence of other STI increased with time from HIV infection, presumably due to reactivation as a result of immunosuppression.

Acute Disease↗

Cost-effectiveness of screening programs for Chlamydia trachomatis: a population-based dynamic approach.

BACKGROUND: Models commonly used for the economic assessment of chlamydial screening programs do not consider population effects. GOAL: To develop a novel dynamic approach for the economic evaluation of chlamydial prevention measures and to determine the cost-effectiveness of a general practitioner-based screening program. STUDY DESIGN: The dynamic approach was used to estimate the cost-effectiveness of a screening program for the first 10 years of screening in The Netherlands. Screening involved a ligase chain reaction test on urine followed by standardized therapies and partner referral. Eligible persons were sexually active, 15 to 24 years, visited a general practitioner, and had no symptoms of sexually transmitted diseases. The heterosexual model population, which consisted of persons 15 to 64 years, had a total chlamydial prevalence of 4.1% before screening. Screening effects on chlamydial incidence were computed by using a population-based stochastic simulation model. Incidence data were connected with a decision analysis model to determine the health effects of the program. The net costs of the program were calculated (investment costs minus averted costs, in 1997 US$) from a societal perspective and expressed per major outcome averted (symptomatic pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility, neonatal pneumonia). RESULTS: Unlike the standard static approach, our model adequately addresses dynamic processes such as chlamydial transmission and the impact of screening programs on chlamydial incidence in the population. During the first 10 years of screening, the investigated program yields savings of US $492 or US $1,086 per major outcome averted, excluding or including indirect costs, respectively. These results depend on chlamydial prevalence and partner referral. CONCLUSIONS: The cost-effectiveness of chlamydial screening programs seems best to be determined by using dynamic modeling on a population basis. In addition to preventing negative health outcomes, the investigated screening program may save costs.

Adolescent↗

Do gender differences in CD4 cell counts matter?

OBJECTIVE: To examine the effect of gender on disease progression and whether gender differences in CD4 lymphocyte counts persisted for the entire course from HIV seroconversion until (death from) AIDS. METHODS: CD4 lymphocyte counts were modelled in 221 female and 443 male seroconverters following seroconversion, backwards from AIDS and backwards from death using regression analysis for repeated measurements. RESULTS: In the period before use of highly active antiretroviral therapy (HAART), progression to AIDS and to death were marginally slower in women than in men as assessed by proportional hazards analysis. Women seroconverted for HIV, developed AIDS and died at higher CD4 cell counts than men (women: 815, 146 and 44 x 10(6) cells/l, respectively; men: 727, 49 and 22 x 10(6) cells/l, respectively), although differences were only statistically significant at AIDS onset. Declines in CD4 lymphocyte counts were not significantly affected by gender and absolute differences between men and women were stable, with exception for the trajectory close to AIDS when the decline became steeper for men than women. CONCLUSION: These gender differences in CD4 lymphocyte counts suggest a delay of initiation of therapy in women compared with men (our model predicted that women reach the threshold of starting HAART at about 12 months later than men). If this delay unfavourably influences progression, treatment guidelines should be revised so that women can benefit equally from HAART.

Acquired Immunodeficiency Syndrome↗

HIV prevalence, sexual risk behaviour and sexual mixing patterns among migrants in Amsterdam, The Netherlands.

OBJECTIVE: To study (1) HIV prevalence; (2) sexual risk behaviour; (3) sexual mixing patterns; (4) determinants of disassortative (between-group) mixing among migrant groups in Amsterdam, the Netherlands and to gain insight into the potential for heterosexual spread of HIV/sexually transmitted diseases. DESIGN: Cross-sectional study among 1660 Surinamese, Antilleans and sub-Saharan Africans, mainly recruited on the streets. METHODS: Saliva was tested for HIV and questions were asked about sociodemographic characteristics, sexual behaviour and the ethnicity of sexual partners. Multivariate logistic regression analysis was used to find predictors for disassortative mixing. RESULTS: HIV prevalence was 1.1% (95% confidence interval: 0.6-1.7). Compared with the Dutch population in general, our study group reported having multiple partners, concurrent partnerships and a history of sexually transmitted diseases much more frequently. Sex in the country of origin during a visit occurred frequently and there was a considerable degree of sexual mixing between different ethnic groups in the Netherlands. For men, disassortative mixing was associated with hard drug use, recent immigration, a high number of partners, being from Nigerian or Hindu-Surinamese origin, a recent sexually transmitted disease and, for steady relationships, consistent condom use. For women, determinants included: hard drug use, low income, being a-religious and, for Antillean and Ghanaian women, consistent condom use. CONCLUSION: Our data suggest a potential for heterosexual spread of sexually transmitted diseases within and between ethnic groups in the Netherlands. The potential for HIV spread is however limited by the low HIV prevalence at present among these groups. This situation may change when HIV prevalence increases in the countries of origin, as bridges exist between those countries and the Netherlands. Culturally appropriate AIDS prevention programmes remain important for these groups.

Adolescent↗

Low levels of hepatitis C virus RNA in serum, plasma, and peripheral blood mononuclear cells of injecting drug users during long antibody-undetectable periods before seroconversion.

Screening of antibodies to hepatitis C virus (HCV) is widely used for monitoring the prevalence of HCV infections and to assess HCV infectivity. Among HCV-infected individuals in the general population, the interval between the detection of HCV RNA and the development of HCV antibodies is usually 5 to 6 weeks, but in rare cases, seroconversion may be prolonged up to 6 to 9 months. In this study, we tested for the presence of HCV RNA during the antibody-undetectable period of 19 drug-injecting HCV seroconverters to gain insight into the antibody-negative carrier status in this population. HCV seroconversion status was determined by testing the first and last serum samples obtained from each subject, using third-generation antibody screening and confirmation assays. Serial samples were tested for HCV-specific antibodies to establish the moment of seroconversion and HCV RNA by single reverse transcriptase-polymerase chain reaction (RT-PCR) and branched DNA assay (bDNA) in serum. Plasma and peripheral blood mononuclear cells (PBMCs) were independently collected and tested for HCV RNA. HCV RNA-positivity was confirmed by Southern blot hybridization and sequencing of serial samples. The 19 HCV seroconverters had a mean follow-up of 5 years (range, 1 to 8 years). Of the 19, 4 were human immunodeficiency virus (HIV)-infected before HCV seroconversion. HCV RNA was detected in serum before seroconversion in 12 (63.2%) of the 19 HCV seroconverters, independent of HIV status. In 7 of these 12, the antibody-undetectable period was relatively short (2 to 10 months). The other 5, who were all HIV-negative before HCV seroconversion, had intermittent low levels of HCV RNA before seroconversion for a period of more than 12 months, with a mean of 40.8 months (range, 13 to 94 months). In all 5 individuals, independent repeats of the experiments confirmed the presence of HCV RNA in serum, and in 3 of these individuals, HCV-positivity was confirmed in independently collected plasma and PBMC samples. Low levels of HCV RNA may be present during prolonged antibody-undetectable periods before seroconversion in a number of injecting drug users. Independent of HIV status, their immune system appears to be unable to respond to these low HCV RNA levels and was sometimes only activated after reinfections with distinct HCV genotypes. These results indicate that primary HCV infection may not always elicit the rapid emergence of HCV antibodies and suggests that persistent low levels of HCV RNA (regardless of the genotype) may not elicit at all or delay antibody responses for prolonged periods of time.

Adult↗

Quantitative antibody responses to structural (Core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: impact of epitope variation and relationship to detection of HCV RNA in blood.

To gain insight into the natural history of hepatitis C virus (HCV), 13 human immunodeficiency virus (HIV)-seronegative injecting drug users were studied who seroconverted for HCV as determined by third-generation enzyme-linked immunosorbent assay, showed an ensuing antibody response to HCV, and were not treated with any antiviral drugs during follow-up. Subjects included 13 untreated HIV-negative individuals, of whom 5 (38.5%) apparently cleared HCV and were polymerase chain reaction (PCR)-negative in at least 3 consecutive samples, 3 (23.1%) showed transient viremia and were PCR-negative in 1 sample during the study period, and the other 5 (38.5%) showed persistent viremia. Viremia was determined longitudinally by reverse-transcription PCR (RT-PCR) and quantified by branched DNA (bDNA). HCV genotypes were determined on serial samples during follow-up. Quantitative antibody levels to core, NS3, NS4, and NS5 were determined using the Chiron RIBA HCV-titering Strip Immunoblot Assay, which is based on HCV genotype 1. The antibody responses to core, NS3, NS4, and NS5 were erratic. In individuals infected with HCV genotype 1, significantly higher median antibody responses to core (P =.02) and to NS4 (P =.04) were found as compared with those infected with other genotypes, showing a significant impact of HCV genotype specificity of the assay. In groups infected with HCV genotype 1, significantly higher median NS3 antibody titers (2.61 relative intensity [RI] vs. 0.38 RI; P =.003) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. In groups infected with genotypes other than genotype 1, significantly higher median NS3 antibody titers (0.89 RI vs. 0.03 RI; P =.0004) and NS5 antibody titers (1.86 RI vs. 0.01 RI; P =.006) were found in the individuals with persistent viremia than in those with apparent resolution of HCV RNA in blood. Individuals with viral persistence had higher HCV-RNA loads with higher antibody responses as compared with individuals with apparent viral clearance from blood. Apparent viral clearance from blood was observed in an unexpectedly high percentage (38.5%), associated with a significant decrease of antibodies to NS3, independent of HCV genotype, as compared with individuals with persistent viremia (P <.005). Apparent viral clearance from blood with gradual loss of antibodies to various HCV proteins, independent of HCV genotype, was observed in 4 of the 5 individuals within approximately 1 year after HCV seroconversion, whereas 1 of these individuals apparently cleared the virus from blood, with complete seroreversion.

Amino Acid Sequence↗

Geographical variation in disease progression in HIV-1 seroconverted injecting drug users in Europe?

BACKGROUND: Human immunodeficiency virus (HIV) disease progression might vary by geographical region due to differences in the spectrum of HIV-related illnesses and (access to) health care. Therefore, the effect of geographical region, next to the effect of other potential cofactors, on disease progression in 664 injecting drug users (IDU) with documented HIV seroconversion from eight cohorts in Europe was studied. METHODS: Kaplan-Meier methods and Cox proportional hazards analysis were performed to assess the effect of geographical region, other sociodemographics, drug use and repeated HIV exposure on progression from HIV seroconversion to immunosuppression, AIDS and death with AIDS. We considered the confounding effect of study-design related factors (e.g. setting of follow-up), and accounted for pre-AIDS death from natural causes by imputing when each endpoint would have occurred, had they not died without AIDS. RESULTS: Estimates of progression to AIDS and death with AIDS were substantially faster after taking pre-AIDS mortality into account. Median incubation time from seroconversion to the first CD4 count < 200 cells/microliter was 7.7 years (95% CI: 7.1-8.3) and to AIDS 10.4 years (95% CI: 9.8-infinity). The 10-year survival was 70.3% (95% CI: 62.8-76.6). The relative hazards (RH) of AIDS for IDU from central and southern Europe compared with IDU from northern Europe was 1.9 (95% CI: 1.2-3.0) and 1.2 (95% CI: 0.6-2.3), respectively, before, and 1.5 (95% CI: 0.7-3.2) and 1.1 (95% CI: 0.6-2.3) after taking differences in study-design related factors into account. Accounting for these factors, the RH of death with AIDS was 0.9 (95% CI: 0.3-2.5) for central and 1.2 (95% CI: 0.4-3.4) for southern Europe compared with northern Europe. For the first CD4 count < 200 cells/microliter these figures were 0.8 (95% CI: 0.5-1.4) and 0.8 (95% CI: 0.5-1.4). Age at seroconversion was the strongest predictor of disease progression. No statistically significant differences in disease progression were found by gender, foreign nationality, drug use and potential repeated HIV exposure. CONCLUSIONS: We found no evidence for regional variability in HIV disease progression among European IDU. Future studies evaluating geographical differences should consider the confounding effect of study-design related factors and differential non-AIDS mortality. As age is an important determinant of disease progression, it should be considered in recommending treatment.

Adult↗

HIV surveillance among sexually transmitted disease clinic attenders in Amsterdam, 1991-1996.

OBJECTIVE: To determine trends in HIV prevalence among attenders of a clinic for sexually transmitted diseases (STD), with emphasis on heterosexuals who did not have a history of injecting drug use. METHODS: Anonymous unlinked HIV surveys with individual consent, conducted each half year from 1991 to 1996 (except 1993) among STD clinic attenders who came for evaluation of a possible new STD episode. RESULTS: Of 10,940 eligible attenders 10,046 (92%) accepted HIV testing. Of all tested attenders, 312 (3.1%) were HIV-infected. Overall HIV prevalence decreased significantly from 4.6% in 1991 to 2.8% in 1996. HIV prevalence among heterosexual men and women who were not injecting drug users was less than 1% in all but one survey period. Except for one woman, none of the 48 HIV-infected heterosexuals was aware of their current serostatus. Among HIV-infected heterosexuals, 21 out of 28 males (75%) and 18 out of 20 females (90%) were of non-Dutch origin. HIV prevalence was 16% among all homosexual men, and 12% among young homosexual men aged < 30 years. HIV prevalence among young homosexual men decreased significantly over time. Among HIV-infected homosexual men, 58% of older men and 59% of younger men were not aware of their current HIV infection. Rates of current STD were generally significantly higher among HIV-infected participants compared with non-HIV-infected participants. CONCLUSIONS: Although HIV prevalence among heterosexual clinic attenders is low, there is a clear potential for ongoing sexual HIV transmission. Most heterosexually acquired HIV infections are found in non-Dutch persons. This observation suggests migration of HIV-infected heterosexuals or the separation of Dutch and non-Dutch heterosexual networks. Awareness of serostatus is almost non-existent among HIV-infected heterosexuals, and is low among male homosexual clinic attenders. To increase awareness of current HIV serostatus and possibly decrease risk behaviour, HIV counselling and testing should be offered actively to all clinic attenders.

AIDS Serodiagnosis↗

Evidence that both HIV and HIV-induced immunodeficiency enhance HCV replication among HCV seroconverters.

The objective of this retrospective cohort study is to assess the mechanism by which human immunodeficiency virus type 1 (HIV) influences hepatitis C virus (HCV) replication in injecting drug users. Virological (HCV and HIV RNA levels) and immunological (CD4+, CD8+ cell counts, and anti-CD3 reactivity) parameters were determined in 19 HCV seroconverters in sequential samples over a period of 1 to 9 years. Among these subjects, 10 were HIV-seronegative (HIVneg), 4 were HIV-seropositive (HIVpos), and 5 seroconverted for HIV (HIVsc) during the observation period. HCV RNA levels were higher in HIVpos subjects than in HIVneg subjects. In subjects seroconverting for HIV, HCV, RNA levels increased significantly immediately after HIV seroconversion (P < 0.0001), while they remained stable over time in HIVpos and HIVneg subjects. HCV RNA correlated inversely with CD4+ cell counts in both the HIVpos population (R = -0.22, P < 0.05) and the HIVneg population (R = -0.45, P < 0.0001). In addition, when subjects were stratified according to CD4+ cell counts a significant difference was found in HCV RNA levels between HIVpos and HIVneg subjects with CD4+ cell counts > 500 cells/microliter (P = 0.001), but not in the population with CD4+ cell counts < 500 cells/microliter. In no population was a correlation found between HCV RNA levels and CD8+ cell counts or anti-CD3 reactivity. Both HIV infection and CD4+ cell counts are apparently associated with HCV RNA levels. The direct association, independent of CD4+ cell counts, between HIV infection and HCV replication appears to be stronger than the association between HIV-induced CD4+ cell decline and HCV replication. We conclude that (i) HCV replication is in some way directly influenced by the presence of HIV; (ii) HCV-specific host immunity controls, in part, HCV replication; and (iii) HCV replication increases when the immune system is impaired by HIV.

CD4 Lymphocyte Count↗

Gender differences in clinical manifestations before AIDS diagnosis among injecting drug users.

We compared incidence rates of self-reported HIV-related symptoms and illnesses, verified clinical manifestations and findings on physical examination between female and male injecting drug users (IDU) stratified by HIV serostatus in the Amsterdam cohort study on the natural history of HIV infection. HIV-positive female IDU (n = 100) reported a higher frequency of several symptoms and illnesses than male IDU (n = 139). Symptoms were reported more chronically by women compared to men, while clinical manifestations were reported by a greater proportion of women affected by these illnesses compared to men. In HIV-negative IDU (163 women and 232 men) the incidence rates were lower compared to HIV-positives, and a similar gender effect on reported symptoms and illnesses was found. Adjusting for biological, behavioral, demographic and study related variables did not change the gender effect on clinical manifestations substantially. We conclude that the gender effect among HIV-positive IDU was not caused by a differential impact of HIV infection on the incidence of the studied clinical manifestations among female and male IDU, but reflects a higher morbidity of female IDU compared to male IDU.

AIDS-Related Opportunistic Infections↗

Hepatitis C virus serotype-specific core and NS4 antibodies in injecting drug users participating in the Amsterdam cohort studies.

In the present study, the RIBA HCV serotyping SIA was evaluated with a cohort of injecting drug users. Serotyping may be a rapid and cost-effective method of determining genotypes in cohort studies. In this study, hepatitis C virus (HCV) antibody-positive sera from a cohort of 331 chronically infected injecting drug users, of which 167 were coinfected with human immunodeficiency virus (HIV), were serotyped by the RIBA HCV Serotyping SIA. Among the 331 specimens, serotype-specific antibodies were detected in 250 (sensitivity, 75. 5%), in which serotype 1 was predominant (57.2%), followed by serotype 3 (26.8%). Among the 331 specimens, 164 were HIV negative, and serotype-specific antibodies were detected in 151 (sensitivity, 92.1%), in which serotype 1 was predominant (59.6%), followed by serotype 3 (33.8%). For a subset of 58 samples taken from 19 chronically infected HCV seroconverters with a mean follow-up of 5 years, serotypes were compared with genotypes, which were determined by a line probe assay (HCV LiPa) and by direct sequencing of the products obtained by nested PCR of the 5' untranslated region. Among the 58 samples with known genotypes, serotype-specific antibodies were detected in 38 (total sensitivity, 65.5%), with a specificity of 78.9%. Thirty of these serotypeable samples revealed a serotype that corresponded to the genotype in the 58 samples (total positive predictive value, 51.7%). Of the 58 samples, 23 were coinfected with HIV, and when these were excluded, the total sensitivity increased to 76.5%, with a total specificity of 80.8% and a total positive predictive value of 61.8%. The serotyping assay showed a high total sensitivity (96.3%) for samples positive by HCV RIBA, version 3.0, with four bands. We conclude that the sensitivity of the RIBA HCV serotyping SIA is limited by the immunocompetence of the HCV-infected host. In general, samples from HIV-negative individuals containing genotype 1a had higher sensitivity, specificity, and concordance in the serotyping assay compared with genotyping, whereas samples containing genotype 3a were found to be more cross-reactive and untypeable. Therefore, the prevalence of genotypes other than genotype 1 could be underestimated if they are determined by serotyping, and improvements in specificity are recommended.

Cohort Studies↗

Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels.

Hepatitis C virus (HCV) infection often persists in association with chronic hepatitis. Different factors have been proposed to determine the clinical outcome of HCV infection. The aim of this study was to examine three different factors of HCV infection among injecting drug users. Nineteen untreated HCV seroconverters were tested longitudinally for the presence of HCV RNA by reverse transcriptase (RT) PCR, and results were quantified by the branched-DNA (bDNA) assay. HCV genotypes were determined with the first sample taken after HCV seroconversion. To assess the natural course of infection, serum alanine aminotransferase (ALT) levels were measured at three stages in every individual. The concordance between bDNA and RT-PCR was 98.9%. Three distinct patterns were found, according to the HCV RNA load after seroconversion during a mean follow-up period of 5 years (range, 1 to 8 years). HCV genotype 1a was predominant (52.6%). There was a significant increase in serum ALT levels (mean 55.5 U/liter) in the early phase of HCV infection, compared with basal serum ALT levels before HCV seroconversion and at the end of the follow-up period. Three distinct HCV RNA load profiles were found, without apparent relationship to genotype and serum ALT levels in the first 5 years of HCV infection.

Alanine Transaminase↗