Introduction
In the last few years HIV test practices have changed in many countries and numbers of persons that seek testing for HIV have increased [1,2] [3–6]
Early diagnosis of HIV infection is important from the individual and the public health viewpoint. At the individual level, knowledge of current serostatus by HIV-infected individuals may lead to receiving education and counselling, and enables them to benefit from prophylaxis for opportunistic infections and antiretroviral treatment [7] [8]
Here we report on HIV testing among patients with sexually transmitted diseases (STD) from 15 countries that contributed to a European multi-centre survey between 1990 and 1996 [9]
Methods
Collection of data
In June 1990, a European survey supported by the Directorate General XII of the Commission of the European Communities was started. The main objective of the survey was to establish a standardized methodology to monitor trends in HIV prevalence in sentinel populations of patients with STD in different geographical regions in Europe [9,10] Chlamydia trachomatis , gonorrhoea, Herpes genitalis , chancroid, syphilis, genital warts, Trichomonas vaginalis , pelvic inflammatory disease and Pediculosis pubis . The minimum diagnostic requirements for the selected STDs have been described previously [9]
Serum specimens were tested for HIV antibodies using commercially available enzyme-linked immunosorbent assays, and seropositive results were confirmed by Western blot or immunofluorescence [9,11]
Statistical analyses
Differences in proportions were tested for statistical significance using χ2 test. Trends were tested for significance using Mantel–Haenszel test for linear association. P -values < 0.05 were considered significant. Incident HIV infections were determined among patients who reported a date (month and year) of a prior HIV-negative test. Patients who reported a year but no month of prior HIV test were assumed to have been previously tested on 1 July of the reported year. Because information on multiple participation was not available systematically, self-reported prior HIV test results were used to analyse knowledge of current serostatus and incident HIV infections.
HIV seroconversion rates were calculated for three arbitrarily constructed European regions (north: Norway, Finland, Sweden, Denmark, The Netherlands; central: Belgium, France, southern Germany, Switzerland, Hungary, Czech Republic; south: Greece, Italy, Spain, Portugal) [12]
Results
Characteristics of patients with STD
Between June 1990 and December 1996, a total of 66 560 patients in whom an STD was diagnosed were tested for HIV antibodies (Table 1 ). Participation in this study was voluntary and generally high (> 90%) although in two centres this percentage was lower (65%). Overall, 6% of eligible patients were not tested for HIV due to reasons other than refusal. The largest proportion of tested patients were heterosexual men (56%), followed by heterosexual women (32%), homosexual men (8%) and IDU (3%). The proportions of IDU and homosexual men were higher in the southern region compared with the central and northern regions. The median age of patients with STD in the southern region (30 years) was higher compared with patients in the central (28 years) and northern (26 years) regions.
Table 1: Distribution of general characteristics, sexually transmitted disease (STD) diagnoses and HIV prevalence among 66 650 patients who participated in the European survey on HIV in STD patients 1990–1996, by European region*.
The distribution of STD diagnoses varied considerably across regions (Table 1 ). The most prevalent diagnosis in the north was (ano)genital chlamydia (27% of all diagnoses in that region) followed by genital warts (24%); in the central region gonorrhoea was most common (16%) and genital warts second (13%); in the south genital warts ranked first with 38% and genital herpes second (11%). Non-specific genital infections (male urethritits, cervicitis) varied from 33% in the north to 24% in the south. Differences in the distribution of STD diagnoses may reflect differences in routine screening for STDs (e.g. chlamydia) or differences in type of STD clinic (e.g. public walk-in clinic, reference clinic) rather than differences in STD prevalence in the respective regions.
HIV infection was identified in 2528 patients with STD (Table 1 ). HIV prevalence was lowest in the north [544 of 26 128; prevalence 2.1%; 95% confidence interval (CI), 1.9–2.3], slightly higher in the central region (657 of 23 789; prevalence 2.8%; 95% CI, 2.6–3.0) but substantially higher in the south (1327 of 16 643; prevalence 8.0%; 95% CI, 7.6–8.4). MSM constituted the largest proportion of HIV-infected patients in the northern (74%) and central regions (56%), but IDU made up the majority (54%) of the HIV-infected patients in the south. Heterosexual men and women accounted for 10 and 5% of all HIV infections in the north, 19 and 11% in the central region and 10 and 12% in the south, respectively.
History of HIV testing
No information on prior HIV tests was available for 2467 (3.7%) patients. Of the total 66 650 patients with STD, 41 727 (62%) reported never having been tested for HIV, with substantial differences in reporting across exposure categories and geographical regions (Table 2 ). For instance, 56% of heterosexual men and 58% of women in the north reported that they had never been tested for HIV compared with 70 and 66% in the central region, and 94 and 84% in the south, respectively. Among heterosexual men, trends over time in this proportion decreased significantly in the north (from 61% in 1990 to 50% in 1995), but remained relatively stable in the central and southern regions. Among heterosexual women, trends decreased significantly in all three regions. Relatively few MSM in the north (38%) and central region (39%) reported to have never been tested for HIV compared with those in the south (72%). This proportion only decreased significantly among homosexual men in the central region. Among IDU, between 28% (in the north) and 46% (in the central region) reported never having been tested for HIV, but no significant trends over time were observed in either of the three regions (Table 2 ).
Table 2: Percentage of 66 650 patients with sexually transmitted diseases (STD)who reported to have never been tested for HIV at entry in the European survey 1990–1996, by HIV exposure category, year of current HIV test in the European survey and European region*.
Knowledge of current HIV serostatus
Knowledge of current HIV serostatus was assessed by relating current HIV test results to self-reported prior HIV test results. Among the 41 727 patients who reported never having been tested for HIV, 611 (1.4%) were HIV infected. Of 20 785 (31%) patients who reported a prior HIV-negative test result, 213 (1.0%) were HIV infected. Thus, at least 824 (33%) of the total 2528 HIV-infected patients were not aware of their current HIV serostatus, either because they had never been tested (n = 611) or they reported a prior HIV-negative test result (n = 213). The majority of these undiagnosed HIV infections were in MSM (46%) and heterosexuals (38%). However, in the south, where 47% of the undiagnosed HIV infections were found, heterosexuals constituted the largest proportion of undiagnosed infections (38%) followed by MSM (34%).
A total of 1581 (2.4%) patients with STD reported a prior HIV-positive test and hence were already aware of their HIV infection at entry in the survey (Table 3 ). Overall, 63% of HIV-infected patients with STD was aware of their current HIV serostatus. This proportion varied considerably across exposure categories: it was 30% among heterosexual men, 52% among heterosexual women, 61% among MSM and 81% among IDU. Substantial regional differences were also observed: for instance, the proportion of aware HIV-infected patients with STD among MSM was lower in the south (50%) than in the north (68%). In contrast, the proportion of aware seropositive patients with STD among IDU was similar in the north and the south (83%), although there were large differences in the absolute numbers (47 versus 597;Table 3 ). In some regions and exposure categories, the proportion of aware HIV-seropositive patients with STD increased over time: significantly trends were observed in the central region among heterosexual men, MSM and IDU. In the south, these proportions increased significantly among MSM and IDU. In the north, the proportion aware HIV-seropositive patients with STD did not change over time in any of the exposure categories (Table 3 ).
Table 3: Number (%) of patients with sexually transmitted disease who reported a prior HIV-positive test among 2528 patients who tested positive for HIV in the European survey 1990–1996, by HIV exposure category, period of current test in the survey and European region*.
Self reported prior HIV tests results and incident HIV infections
A total of 20 785 patients with STD reported a prior HIV-negative test. Incident HIV infections were determined among the 11 684 (56%) patients who were also able to report a test date. Among these 11 684 STD patients, 108 HIV infections were found, representing 51% of the total of 213 HIV infections found among patients with STD who reported a prior HIV-negative test. The rate of incident HIV infections among patients who did and did not report a test date was statistically not significantly different (0.9 versus 1.1%, P > 0.05).
Among the 11 684 patients who reported a test date, the mean number of months since the last HIV test was 18 (median 12, range 1–134), but this number was substantially higher among seroconverters (mean 28 months; median 22.5, range 1–94). The number of seroconversions were 38, 22 and 48 in the northern, central and southern region, respectively. The seroconversion rate was higher in the southern region (3.8%) compared with the northern (0.5%) and central region (0.7;P < 0.001;Table 4 ). Half (n = 57) of the total incident HIV infections were found among MSM. In the northern and central region the prevalence of seroconversions was significantly higher among MSM (4.7 and 5.2%, respectively) compared with IDU (0.9 and 1.4%) or heterosexual men (0.1 and 0.2%) and women (0.2 and 0.2%). However, in the southern region the highest seroconversion rate was found among IDU (10.9%). Overall, incident HIV infections were significantly more often found among patients aged 30 years or older compared with those aged under 30 years (P < 0.001). However, this age effect was not seen in the southern region. In all three geographical regions we found no significant association between seroconversion and the type of STD (bacterial, viral or other) nor between seroconversion and the survey period (before 1994 compared with 1994 or later, Table 4 ).
Table 4: Number (%) of incident HIV infections and univariate associates of HIV seroconversion (SC) among 11 684 STD patients who were tested for HIV in the European survey 1990–1996, and who reported a date of prior HIV negative test, by European region*.
Multivariate logistic regression analyses were performed to adjust for the potential confounding effects of the variables listed in Table 4 that were significantly associated with HIV seroconversion (Table 5 ). In this model, the adjusted risk of HIV seroconversion was 4.4-fold higher in the south and 1.2-fold higher in the central region compared with the north. Compared with heterosexual men, the risk of HIV seroconversion was higher, although statistically not significant, among heterosexual women [adjusted odds ratio (OR), 1.67]; however, it was much higher among homosexual men (adjusted OR, 15.29) and IDU (adjusted OR, 9.28). In this model, age was no longer significantly associated with HIV seroconversion. Analyses of interactions between the variables included in the final model indicated a higher risk of HIV seroconversion among IDU aged under 30 years and a lower risk of seroconversion among homosexual men in the southern region. No significant interactions were found between age and region.
Table 5: Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for HIV seroconversion among 11 684 patients with sexually transmitted disease (STD) who reported a date of a prior HIV negative test and who were tested for HIV in a European multicentre survey, 1990–1996.
Discussion
The objectives of the present study among patients with STD in Europe were three-fold. First, to assess trends in HIV test seeking behaviours and knowledge of current serostatus; second, to determine trends in clinic-visits of aware HIV-seropositive patients; and third, to estimate the HIV incidence among patients with a prior HIV-negative test.
The proportion of patients with STD who reported to have ever been tested for HIV prior to participation in this survey was 34% overall and 38% in 1996, the last survey year. This proportion differed greatly across European regions and generally was lowest in the south in all exposure categories except IDU. For instance, only 5–7% of male heterosexual patients with STD in the south reported a prior HIV test compared with 28% in the central region and 50% in the north. These differences in prior test rates may be due to differences in availability or accessibility of HIV testing in European countries [13,14] [2,3]
In the absence of an effective HIV vaccine, counselling and testing is the primary means for prevention of HIV infection. Therefore, low threshold HIV testing facilities should be readily accessible for those who request HIV counselling and testing; reducing fear and increasing knowledge about HIV risks remain ongoing essential elements of effective HIV prevention programmes. The data from this survey support the notion that confidential HIV testing should be actively offered to all those who present for examination of STD-related complaints [15,16] [17]
As a public health measure, increased awareness of HIV serostatus may limit the sexual transmission of HIV, because persons who are aware of their HIV infection may receive antiretoviral treatment resulting in reduced genital shedding of HIV-1 [8,18] [19–22] [19] [8,23–25]
Of all HIV infections found in this survey, 8% were in patients who reported a prior HIV-negative test and 24% in patients who had never been tested for HIV. These HIV infections remained largely undiagnosed because in most countries the test results were not given to survey participants. The proportions of undiagnosed HIV infections were quite similar across the three European regions, but there were differences within exposure categories. The highest proportion of undiagnosed infections was among heterosexual men (66%) and women (48%); lower proportions were found among homosexual men (39%) (young 42%) and IDU (19%). Among heterosexual women this proportion was highest in the north (65%), among homosexual men it tended to increase from north (30%) to central (40%) to south (50%), and among IDU it was much higher in the central region (43%) compared with the north and south. These proportions reflect regional levels of missed opportunities for counselling, safe sex education and referral for antiretroviral treatment. They also reflect the level to which the testing practices in these regions and exposure groups are sufficiently targeted to populations at risk for HIV.
Several observations in this survey suggest that MSM and IDU play a major role in sexual transmission of HIV. First, rates of HIV incidence were highest among MSM, in particular among men aged under 30 years (data not shown). Second, HIV prevalence among patients with STD in southern Europe who inject drugs was 57%. Relatively high prevalence rates were also found among young MSM, varying from 15% in the south to 19% in central and north Europe; in central Europe the HIV prevalence among young MSM was about three times as high as among older men. These data are a cause for concern and clearly indicate that (young) MSM and IDU continue to play a major role in the ongoing sexual transmission of HIV [26–28]
Some limitations to the present study need clarification. First, in regions where HIV testing is not easily accessible, limited numbers of patients are able to report prior HIV test results and therefore could not be included in the incidence estimation. In addition, among the participants who reported a prior HIV-negative test, only 56% was able to also report a test date. Among these 56% we found 51% of the total number of HIV infections, suggesting that the estimated rate of seroconversion is fairly representative for all participants with a prior HIV-negative test. Second, our results may have been biased by multiple participation of patients who reported a prior HIV-negative test and who tested positive for HIV in the survey. Since this survey is anonymous and most participants remained unaware of their test results, such multiple participation could result in overestimation of the HIV seroconversion. To minimize this potential bias, we re-analysed incident HIV cases based on a selection of participants with seroconversion intervals of 2 years or less, which showed a fairly similar result This observation suggests that participation of persons with longer seroconversion intervals, and also multiple participation of patients who report a prior HIV-negative test and who tested positive for HIV in the survey probably did not bias our results. Third, because reasons for not testing were not systematically collected, analyses of non-testers were carried out irrespective of the reason for not testing. Our results may have been biased because of non-testing, but the direction of this bias is unknown. Finally, because of limited numbers of seroconverters, analyses based on finer sub-division of regions (e.g. countries, sites) are not presented here. The division of Europe into three regions was made arbitrarily. Although some of the countries placed together in each of the three European regions may be quite similar in terms of STD control or accessibility of HIV testing, the data presented may not reflect the situation in all sites and countries included in each region.
Although the degree to which a convenience sample is representative of a broadly defined population is, in part, a matter of informed judgement, some conclusions can be drawn. We found large numbers of undiagnosed HIV infections in patients with STD who were never tested for HIV. Selectively offering HIV testing to STD clinic attenders based on risk assessment may miss many HIV-infected subjects; therefore, HIV testing should be offered to all individuals attending STD clinics [15,16]
The HIV epidemic in Europe is now at an important turning point. In western Europe, AIDS incidence has been declining since 1996, partly as a result of more effective treatment of HIV infection. Therefore, AIDS incidence data have become of limited value for reliably tracking the HIV epidemic [1,7]
Acknowledgements
The authors wish to thank the participating clinics, the national co-ordinators and their teams, and the international experts who have contributed to this European Concerted Action, and are grateful for the suggestions and critical comments of Maria Prins and Roel Coutinho.
References
1. Hamers FF, for the group of experts and national coordiators of HIV/AIDS surveillance from the countries of the WHO European Region. Eurosurveillance 1998, 3: 51. 51.
2. Anon.
HIV testing among populations at risk for HIV infection – nine states, November 1995 – December 1996. MMWR 1998, 47: 1086 –1091.
3. Couturier E, Schwoebel V, Michon C. et al.
Determinants of delayed diagnosis of HIV infection in France, 1993-1996. AIDS 1998, 12: 795 –800.
4. Anon.
HIV/AIDS Surveillance in the European Union. Quarterly report No. 38, 31 March 1997 . Paris: European Centre for the Epidemiological Monitoring of AIDS; 1997.
5. Wortley PM, Chu SY, Diaz T. et al.
HIV testing patterns: where, why, and when were persons with AIDS tested for HIV. AIDS 1995, 9: 487 –492.
6. Poznanzky MC, Coker R, Skinner C. et al.
HIV positive patients first presenting with an AIDS defining illness: characteristics and survival. BMJ 1995, 311: 156 –158.
7. Carpenter CCJ, Fischl MA, Hammer SM. et al.
Antiretroviral therapy for HIV infection in 1997. JAMA 1998, 280: 78 –86.
8. Vernazza PL, Eron JJ, Fiscus SS. et al.
Sexual transmission of HIV: infectiousness and prevention. AIDS 1999, 13: 155 –166.
9. The European Study Group.
European Community Concerted Action on HIV seroprevalence among sexually transmitted disease patients in 18 European sentinel networks. AIDS 1993, 7: 393 –400.
10. van der Heyden J, Batter V, Sasse A, Stroobant A and the European Study Group for HIV infections in sentinel populations of STD patients.
Final results 1990–1996. Brussels, Belgium: Scientific Institute of Public Health – Louis Pasteur; 1997.
11. Batter V, Stroobant A, and the European Study Group on HIV in STD patients.
Trends in HIV seroprevalence among persons with sexually transmitted diseases in 17 European sentinel networks 1990–1996. AIDS 2000, 14: 871 –880.
12. Lundgren JD, Phillips AN, Vella S. et al.
Regional differences in use of antiretroviral agents and pryimary prophylaxis in 3122 European HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1997, 16: 153 –160.
13. Infuso A, Hamers F.
HIV testing in Europe: marked differences in policies and practices. XII International Conference on AIDS , Geneva, Switzerland, June 1998 [abstract 42119].
14. Anon.
HIV testing and HIV case reporting in Europe. Paris: European Centre for the Epidemiological Monitoring of AIDS; 1998.
15. Chen Z, Branson B, Ballenger A, Peterman TA.
Risk assessment to improve targeting of HIV counselling and testing services for STD clinic patients. Sex Trans Dis 1998, 25: 539 –543.
16. Fennema JSA, van Ameijden EJC, Coutinho RA. et al.
HIV surveillance among sexually transmitted diseas clinic attenders in Amsterdam, 1991–1996. AIDS 1998, 12: 931 –938.
17. Samet JH, Freedberg KA, Stein MD. et al.
Trillion virion delay: time from testing positive for HIV to resentation for primary care. Arch Intern Med 1998, 158: 734 –740.
18. Wainberg MA, Friedland G.
Public health implications of antiretroviral therapy and HIV drug resistance. JAMA 1998, 279: 1977 –1983.
19. Marks G, Burris S, Peterman TA.
Reducing sexual transmission of HIV from those who know they are infected: the need for personal and collective responsability. AIDS 1999, 13: 297 –306.
20. Chamot E, Laborde D, Rice JC.
Do HIV testing and counseling increase risk behaviour ? Am J Public Health 1995, 85: 1297 –1298.
21. Cohen DA.
The efficacy of testing and counseling in limiting HIV transmission. Am J Public Health 1994, 84: 321. 321.
22. Otten MW, Zaidi AA, Wroten JE. et al.
Changes in sexually transmitted disese rates after HIV testing and posttest counseling. Am J Public Health 1993, 83: 529 –533.
23. Fleming DT, Wasserheit JN.
From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Trans Dis 1999, 75: 3 –17.
24. Taha TE, Hoover DR, Dallabetta GA. et al.
Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998, 13: 1699 –1706.
25. Grosskurth H, Mosha F, Todd J. et al.
Impact of improved treatment of sexually tranmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995, 346: 530 –536.
26. Weinstock HS, Sweeney S, Satten GA. et al.
HIV seroincidence and risk factors among patients repeatedly tested for HIV attending sexually transmitted disease clinics in the United States, 1991 to 1996. J Acquir Immune Defic Syndr Hum Retrovirol 1998, 19: 506 –512.
27. Buchbinder SP, Douglas JM, McKirnan DJ. et al.
Feasibility of HIV vaccin trials in homosexual men in the United States: risk behavior, seroincidence and willingness to participate. J Infect Dis 1996, 174: 954 –961.
28. Catchpole MA, Mercy DE, Nicoll A. et al. on behalf of the Collaborative Group.
Continuing transmission of sexually transmitted diseases among patients infected with HIV-1 attending genitourinary medicine clinics in England and Wales. BMJ 1996, 312: 539 –542.
Appendix
The European Study Group for HIV in STD patients
Co-ordinating team: A. Stroobant, V. Batter, J. van der Heijden, A. Sasse (Belgium); M. Bruckova, B. Kriz (Czech Republic); A.M. Worm, E. Smith (Denmark); A. Ponka (Finland); L. Meyer (France); S. Golsch (Germany); M. Hadjivassiliou-Pappa, M. Vounatsou (Greece); M. Guiliani, B. Suligoi (Italy); R. Chin-A-Lien, W.I. van der Meijden, J.S.A. Fennema, J.A.R van den Hoek (The Netherlands); H. Moi (Norway); J Cardoso, I. Santos (Portugal); I. de la Mata (Spain); C. Anagrius (Sweden); J. Paget (Switzerland).
