1 SUPPLEMENT ARTICLE Trends in Human Immunodeficiency Virus Infection among Drug Users in a Detoxification Unit Roberto Muga, Arantza Sanvisens, José Manuel Egea, Jordi Tor, and Celestino Rey-Joly Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain In a cross-sectional study of 1111 injection drug users (IDUs) admitted to a hospital detoxification unit between 1987 and 2001, characteristics of substance abuse and blood samples were obtained at study entry. The median age at admission was 27 years, the median age at first injection of drugs was 19 years, and the median duration of injection drug use was 84 months. Overall prevalence of human immunodeficiency virus (HIV) infection was 60% (58% in men, 66% in women; P p.026). Age at start of and duration of injection drug use were associated with HIV infection ( P!.001). The rate of HIV infection in persons with short duration of drug use (!24 months) was higher among women (45%) than among men (21%) ( P p.002). The prevalence of HIV infection among IDUs!21 years old at first use of injection drugs and among patients reporting!48 months of injection drug use was significantly lower in those who started injection drug use after 1992 (19% vs. 53% of IDUs; odds ratio, 4.42; 95% confidence interval, ). Awareness of acquired immunodeficiency syndrome, preventive measures, and substance abuse treatment have contributed to the stabilization of the HIV epidemic. The higher prevalence of HIV infection among women IDUs and among young IDUs who recently began injecting drugs emphasizes the need to target HIV-transmission risk reduction interventions early. Since 1981, a total of 61,028 people have received a diagnosis of AIDS in Spain . In fact, the pairing of drug abuse and HIV infection is one of the most critical public health problems in our country because every 2 out of 3 AIDS cases are related to injection drug use. The sudden onset of the HIV epidemic coincided with the spread of injection heroin use in Spain in the late 1970s [2, 3]. The expansion of injection heroin use and the lack of knowledge of the modes of HIV transmission was of fundamental importance to the spread of HIV at the beginning of the 1980s; by 1993, Spain had the highest cumulative incidence of AIDS cases in Western Europe. Grant support: Fondo de Investigación Sanitaria (FIS), Ministry of Health, Spain (FIS 00/0294, FIS G03/005). Reprints or correspondence: Dr. Roberto Muga, Dept. of Internal Medicine, Rm. 806, Hospital Universitari Germans Trias i Pujol, Carretera Canyet s/n, Badalona, Barcelona, Spain Clinical Infectious Diseases 2003; 37(Suppl 5):S by the Infectious Diseases Society of America. All rights reserved /2003/3712S5-0014$15.00 Previous studies have demonstrated that 2 groups, injection drug users (IDUs) who start injection drug use at an early age and women, are at increased risk of HIV infection, even in areas where extensive prevention and harm reduction programs have been implemented [4 9]. From a public health perspective, the monitoring of the prevalence of HIV infection and the identification of target groups of young IDUs who recently started injecting drugs are essential for the development of effective health interventions . In our setting, the scarcity of prospective studies on the incidence of HIV infection reinforces the need to analyze the temporal trends of prevalence. Furthermore, the decrease in the number of cases of AIDS in Spain since 1997 may be attributed not just to the introduction of HAART but also to a lower rate of infection among IDUs, because injection drug use is the main route of HIV transmission. The objective of this study was to monitor trends in the prevalence of HIV infection in a hospital detoxification unit where IDUs with the most severe patterns of drug use were referred over the last 15 years. S404 CID 2003:37 (Suppl 5) Muga et al.
2 PATIENTS, MATERIALS, AND METHODS Study design and study population. This was a cross-sectional study of IDUs admitted to a 4-bed detoxification unit in a tertiary hospital in Badalona (metropolitan Barcelona) between February 1987 and December Patients were referred from outpatient clinics for substance abuse treatment. Further details regarding the criteria for admission and the characteristics of detoxification treatment have been published elsewhere . Briefly, the majority of subjects included in this study were heroin users who injected the drug an average of 3 times a day and showed clear criteria of heroin dependence. At admission, subjects provided blood samples for determination of HIV (confirmed by EIA and Western blot), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg), and syphilis (confirmed by rapid plasma reagin [RPR] and microhemagglutination [MHA-TP] tests) and completed an interviewer-administered (face-to-face) questionnaire regarding demographic and drug use characteristics. Date of and age at first injection of drugs and duration of injection drug use were specifically asked for during the interview. For the purpose of this study, patients who were admitted to the detoxification unit 11 time between 1987 and 2001 were assessed only at their first admission. Statistical analysis. Data analysis was done with Student s t test or analysis of variance and the x 2 test. The magnitude of the univariate associations for HIV infection and variable predictors were measured by odds ratios with 95% confidence intervals. P!.05 was considered statistically significant. Statistical analysis was done with SPSS version 11.5 (SPSS) and Epi Info version 6 (Centers for Disease Control) packages. RESULTS Table 1. Characteristics of 1111 injection drug users at admission to a hospital detoxification unit, February 1987 to December Characteristic Value Sex Male 903/1111 (81) Female 208/1111 (19) Injection drug use a Age at start, median years 19 Date of start, median May 1985 Duration, median months 84 Age at hospital admission, median years 27 Infection status HIV positive 661/1111 (60) HCV positive b 325/354 (92) HBsAg positive 77/973 (8) Positive for syphilis 23/691 (3) NOTE. Data are no. of patients with characteristic/no. tested (%), unless indicated otherwise. HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus. a Data for 1104 patients. b Testing for HCV antibodies was done after September From February 1987 through December 2001, 1144 IDUs were admitted to the detoxification unit. Thirty-three patients (2.9%) did not provide a blood sample to test for HIV, so the population of the study was 1111 patients. Of these, 39% of patients had been incarcerated before admission. Seventy-nine percent of patients reported a temporary cessation of injection drug use (median duration of cessation, 14 months; interquartile range [IQR], 6 34 months). For 7 of the 1111 cases, we do not have information regarding age at and date of first injection of drugs and duration of injection drug use. Thirty-four percent of patients began injection drug use at age!18, 35% between the ages of 18 and 21, and 31% at age 21. The duration of injection drug use before admission was!24 months for 16% of the patients, months for 16%, and 148 months for 68%. Table 1 shows the characteristics of the patient population at entry: 81% of patients were men, the median age at admission was 27 years (IQR, years), and the median duration of injection drug use was 84 months (IQR, months). Globally, 60% of patients were HIV-positive, 92% were HCV-positive, 8% were HBsAg-positive, and 3% had positive results of RPR and MHA-TP testing. HIV-positive IDUs had started injection drug use earlier (mean, January 1984) than had those who were HIV-negative (mean, June 1988). The proportion of women was higher among HIV-positive subjects than among those who were HIVnegative (21% vs. 16% of patients; P p.03). Patients age at the start of injection drug use was younger among HIV-positive IDUs than among HIV-negative IDUs (mean ages, vs years; P!.001). Also, the duration of injection drug use was significantly longer among HIV-positive IDUs than among those who were HIV-negative (mean duration, vs months; P!.001). The prevalences of HCV infection and of positive serologic test results for syphilis (as determined by RPR and MHA-TP tests) were significantly higher in HIV-positive IDUs (98% and 4% of patients, respectively) than in HIV-seronegative IDUs (86% and 2%) ( P!.001). Prevalence of HBsAg positivity was similar in HIV-positive (8% of patients) and HIV-negative (7%) IDUs ( P p.47). As determined by use of similar recruitment strategies and interviewer-administered questionnaires, the characteristics of patients have changed over the last 15 years. Age at the start of injection drug use, duration of injection drug use, and age at admission have significantly increased for those admitted between 1997 and 2001 (table 2). However, the proportion of male IDUs remained stable and the prevalence of HIV de- HIV Infection Trends among IDUs CID 2003:37 (Suppl 5) S405
3 Table 2. Characteristics of 1111 injection drug users at admission to a hospital detoxification unit, by calendar periods of admission, February 1987 to December Characteristic (n p 491) Period of admission (n p 390) (n p 230) Male, % of patients Date of birth, mean May 1963 Jan 1966 Jan 1968!.001 Injection drug use Age at start, mean years !.001 Duration, mean months !.001 Age at admission, mean years !.001 Infection status, % of patients HIV positive !.001 HCV positive NA 93 b HBsAg positive Positive for syphilis NOTE. HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; NA, not available. a P for comparison of calendar periods of admission. b Testing for HCV antibodies was performed after September P a creased from 70% to 48%, despite the fact that the patients admitted between 1997 and 2001 had a longer duration of injection drug use. In relation to year of first injection of drugs, 61.4% of subjects (678 of 1104 patients) started using injection drugs before 1987, whereas 13.7% (151 of 1104) started after Table 3 shows the association of HIV-infection prevalence with calendar periods of start of injection drug use (!1987, , 11992), sex, and age at first injection of drugs. Despite a significant decrease in the prevalence of HIV infection in the period later than 1992, 25% of those IDUs who started injection drug use before the age of 18 and 35% of the women with short duration of injection drug use were HIV positive. Figures 1 3 show the downward trend in HIV-infection prevalence with regard to the year of starting injection drug use, sex, and age at first injection drug use in persons with comparable durations of injection. Patients starting injection drug use after 1992, men, and persons 121 years old when they started using injection drugs show less prevalence of HIV infection than do those starting before 1992, females, and IDUs!18 years old when they began using injection drugs. Table 4 shows the odds of being HIV positive according to sex and age at start of injection drug use, after controlling for the duration ( 48 months or 148 months) and the calendar period (1992 and before, or after 1992) of injection drug use. IDUs who reported 14 years of injection drug use and first parenteral use of Table 3. Prevalence of HIV infection among 1111 injection drug users at admission to a hospital detoxification unit in 3 calendar periods, according to sex and to age at the start of injection drug use. Characteristic No. (%) of patients positive for HIV, by period injection drug use started Before 1987 (n p 678) (n p 275) After 1992 (n p 151) Sex Male 402 (74) 96 (42) 22 (18)!.001 Female 100 (76) 27 (56) 9 (35)!.001 Age at start of injection drug use, years! (76) 36 (54) 4 (25)! (77) 44 (43) 9 (27)! (64) 43 (40) 18 (18)!.001 a P for comparison of periods of starting injection drugs. P a S406 CID 2003:37 (Suppl 5) Muga et al.
4 Figure 1. Prevalence of HIV (% of patients infected) according to calendar periods of start of injection drug use and duration of injection drug use. (*), P for comparison of HIV-infection prevalence by period of starting injection drug use within same category of duration (i.e., for those reporting 14 years of injection drug use, prevalence of HIV was 76% if they started injecting before 1987, 49% if they started between 1987 and 1992, and 33% if they started after 1992; P p.003). (**), P for comparison of HIV-infection prevalence by period of starting injection drug use according to 3 categories of duration of injection drug use (i.e., prevalences of HIV in those starting injection drug use before 1987 and reporting 14 years, 2 4 years, or!2 years of injection drug use were 76%, 60%, and 48%, respectively; P p.001). drugs before 1992 had an increased probability of being HIVpositive than did those with similar characteristics who started injecting drugs after 1992 (OR, 5.39; 95% CI, ). DISCUSSION During 15 years, we have monitored the prevalence of HIV in hard-line IDUs, which has allowed us to confirm the stabilization of the epidemic regarding the main category of transmission in Spain. In this respect, the decrease in the number of cases of AIDS in Spain since 1997 may have not been due merely to the effectiveness of HAART but also to the reduction in the number of new HIV-infected IDUs. Recently, the European Monitoring Centre for Drugs and Drug Addiction (Lisbon) has reported similar trends in HIV infection among Span- Figure 2. Prevalence of HIV (% of patients infected) according to sex and duration of injection drug use. (*), P for comparison of HIV-infection prevalence in men and women within same category of duration (i.e., for those reporting 14 years of injection drug use, prevalence of HIV was 76% in women vs. 69% in men; P p.095). (**), P for comparison of HIV-infection prevalence by sex according to 3 categories of duration of injection drug use (i.e., prevalences of HIV in women reporting 14 years, 2 4 years, or!2 years of injection drug use were 76%, 53%, and 45%, respectively; P p.001). HIV Infection Trends among IDUs CID 2003:37 (Suppl 5) S407
5 Figure 3. Prevalence of HIV (% of patients infected) according to age at start of injection drug use and duration of injection drug use. (*), P for comparison of HIV-infection prevalence by age at starting injection within same category of duration (i.e., for those reporting 14 years of injection drug use, prevalence of HIV was 74% if they started injection at age!18 years, 71% if they started at age years, and 61% if they started at age 121 years; P p.026). (**), P for comparison of HIV-infection prevalence by age at starting injection according to 3 categories of duration (i.e., prevalences of HIV in those starting injection at age!18 years and reporting 14 years, 2 4 years, or!2 years of injection drug use were 74%, 54%, and 41%, respectively; P p.001). ish drug users . If the findings of this study regarding the prevalence of HIV relate to heavy users of injection drugs, it is probable that persons with less-severe patterns of drug abuse will show a similar reduction. Of note, the decrease in the prevalence of HIV infection is not observed in other common bloodborne infections, such as HCV, or in the percentage of chronic carriers of HBsAg. We found a consistent and gradual downward trend in HIVinfection prevalence in IDUs who began injection drug use after 1992, regardless of the age at first injection drug use and of sex, and in persons with comparable durations of injection drug use. In that year, programs of methadone substitution treatment for heroin dependence started to be generalized in the city of Barcelona, and that intervention has been one of the major initiatives in diminishing the spread of HIV [13, 14]. Despite the decrease in the prevalence of HIV infection, we Table 4. ORs for HIV infection in a cohort of 1111 injection drug users according to sex and age at start of injection drug use. Characteristic, period injection drug use started OR (95% CI) for HIV infection, by duration of injection drug use 48 months 148 months Age at start of injection drug use 21 years Before or during ( ) 4.14 ( ) 121 years Before or during ( ) 5.39 ( ) Sex Male Before or during ( ) 2.29 ( ) Female Before or during ( ) 2.73 ( ) S408 CID 2003:37 (Suppl 5) Muga et al.
6 identified 2 subsets of persons who deserve special attention because they maintain a relatively high prevalence of HIV: women and those IDUs who started injection at a young age. During the first 2 years of injection drug use, women have more than twice the prevalence of HIV infection that male IDUs have, and these differences were similar before and after The explanation for the excess of infection has been related to the high frequency of exchanging drugs for sex [15, 16] and/or of having a sex partner who is also an IDU . Concerning the age of starting drug use, those who start at a younger age always show a higher prevalence of HIV. Young age is associated with high-risk behavior related to drug use, and in this regard, to delay the age of starting drug use can be favorable to the acquisition of habits that prevent the transmission of bloodborne infections [18 20]. Several limitations should be noted in this study. The external validity and generalization of results can be limited when only a single treatment center is taken into account to analyze the evolution of the HIV epidemic. In this hospital cohort, a bias in survival is possible because of the fact that IDUs could die from AIDS or overdose before admission. Last, some patients cannot assess the date when they started injection drug use, in particular those IDUs with chronic, long-term addiction. However, the recall bias is not usually observed among those who have injected drugs for only a few years. From this study, we can infer the necessity for implementing preventive interventions for female IDUs and for those young and recent initiates. Early diagnosis of the addiction, promoting harm reduction in HIV prevention, and treatment for drug abuse are effective ways to curtail the spread of HIV infection. References 1. Vigilancia epidemiológica del VIH/sida en España. Actualización a 30 de junio de Parte I. 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