Pre‐AIDS mortality from natural causes associated with HIV disease progression: evidence from the European Seroconverter Study among injecting drug users

Objectives:To study differences in pre-AIDS mortality between European cohorts of injecting drug users (IDU) and to evaluate whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count. Methods:The study population consisted of 664 IDU with documented intervals of HIV seroconversion from eight cohort studies. Differences in pre-AIDS mortality were studied between European sites; an evaluation of whether pre-AIDS mortality increased with time since HIV seroconversion and decreasing CD4 count was carried out using Poisson regression. Results:One hundred and seven IDU died, of whom 57 did not have AIDS. Pre-AIDS causes of death were overdose/suicide (49%), natural causes such as bacterial infections/cirrhosis (40%), and unintentional injuries/unknown (11%). Considering pre-AIDS death and AIDS as competing risks, 14.7% were expected to have died without AIDS and 17.3% to have developed AIDS at 7 years from seroconversion. No statistically significant differences in pre-AIDS mortality were found between European regions, men and women, age categories and calendar time periods. Overall pre-AIDS mortality did not increase with time since seroconversion, but did increase with decreasing CD4 count. Evaluating cause-specific mortality, only pre-AIDS mortality from natural causes appeared to be associated with time since seroconversion as well as immunosuppression. For natural causes, the death rate per 100 person-years was 0.13 the first 2 years after seroconversion, 0.73 in years 2–4 [risk relative (RR) to years 0–2, 5.6], 1.83 in years 4–6 (RR, 14.0) and 1.54 for ≥ 6 years (RR, 11.7). This rate was 0 for a CD4 cell count ≥ 500 × 106/l, 1.06 for 200–500 × 106/l and 4.06 for < 200 × 106/l (RR versus ≥ 200 × 106/l, 7.0). In multivariate analysis, both CD4 count and time since seroconversion appeared to be independently associated with death from natural causes; CD4 count appeared to be the strongest predictor (adjusted RR, 5.9). Conclusions:A high pre-AIDS mortality rate was observed among IDU. No significant differences were observed across European sites. Pre-AIDS mortality from natural causes but not from overdose and suicide was associated with HIV disease progression.

[1]  J. Goudsmit,et al.  Prevalence and risk factors of HIV infections among drug users and drug-using prostitutes in Amsterdam. , 1988, AIDS.

[2]  Geurt Jongbloed,et al.  The Iterative Convex Minorant Algorithm for Nonparametric Estimation , 1998 .

[3]  C. Rizza,et al.  Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population , 1996, The Lancet.

[4]  R. Brettle,et al.  Human immunodeficiency virus and drug misuse: the Edinburgh experience. , 1987, British medical journal.

[5]  D. Fuchs,et al.  Trends in HIV infection among intravenous drug users in Innsbruck, Austria. , 1992, Journal of acquired immune deficiency syndromes.

[6]  D. Vlahov,et al.  Impact of HIV infection on non‐AIDS mortality among Italian injecting drug users , 1994, AIDS.

[7]  Niels Keiding,et al.  Statistical Models Based on Counting Processes , 1993 .

[8]  M. Rahman,et al.  Mortality and survival among a cohort of drug injectors in Glasgow, 1982-1994. , 1997, Addiction.

[9]  J M Taylor,et al.  Replacing time since human immunodeficiency virus infection by marker values in predicting residual time to acquired immunodeficiency syndrome diagnosis. Multicenter AIDS Cohort Study. , 1996, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[10]  P. Selwyn,et al.  Clinical manifestations and predictors of disease progression in drug users with human immunodeficiency virus infection. , 1992, The New England journal of medicine.

[11]  R. Coutinho,et al.  Predictors of mortality in the Amsterdam cohort of human immunodeficiency virus (HIV)-positive and HIV-negative drug users. , 1996, American journal of epidemiology.

[12]  R. Park.  European AIDS definition , 1992, The Lancet.

[13]  C. Sabin,et al.  Acquired immunodeficiency syndrome (AIDS) risk in recent and long-standing human immunodeficiency virus type 1 (HIV-1)-infected patients with similar CD4 lymphocyte counts. , 1993, American journal of epidemiology.

[14]  G. H. Mientjes,et al.  Death from suicide and overdose among drug injectors after disclosure of first HIV test result , 1994, AIDS.

[15]  P. Selwyn,et al.  Impact of the AIDS epidemic on morbidity and mortality among intravenous drug users in a New York City methadone maintenance program. , 1989, American journal of public health.

[16]  J. Wellner,et al.  Information Bounds and Nonparametric Maximum Likelihood Estimation , 1992 .

[17]  C. Rouzioux,et al.  Effect of age and exposure group on the onset of AIDS in heterosexual and homosexual HIV‐infected patients , 1994 .

[18]  P. Magnus,et al.  Differences in mortality rates and causes of death between HIV positive and HIV negative intravenous drug users. , 1993, International journal of epidemiology.

[19]  M. Musicco,et al.  Mortality of intravenous drug users living in Milan, Italy: role of HIV‐1 infection , 1994, AIDS.

[20]  D. Goldberg,et al.  A system for surveillance of voluntary HIV testing: results of the first 2 years, 1989-1990. , 1992, AIDS.

[21]  F. Forastiere,et al.  Mortality of intravenous drug users in Rome: a cohort study. , 1991, American journal of public health.

[22]  I. Hernández-Aguado,et al.  Determinants of HIV-1 infection in intravenous drug users in Valencia, Spain, 1987-1991. , 1993, International journal of epidemiology.

[23]  Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. , 1987, MMWR supplements.

[24]  S. Friedman,et al.  HIV infection and intravenous drug use: critical issues in transmission dynamics, infection outcomes, and prevention. , 1988, Reviews of infectious diseases.

[25]  R. Hammersley,et al.  Drugs associated with drug-related deaths in Edinburgh and Glasgow, November 1990 to October 1992. , 1995, Addiction.

[26]  J. Antó,et al.  Mortality trends in a cohort of opiate addicts, Catalonia, Spain. , 1996, International journal of epidemiology.

[27]  A. Phillips,et al.  CD4 lymphocyte count as a determinant of the time from HIV seroconversion to AIDS and death from AIDS: evidence from the Italian Seroconversion Study , 1994, AIDS.

[28]  D. Mildvan,et al.  A larger spectrum of severe HIV-1--related disease in intravenous drug users in New York City , 1988, Science.

[29]  Maria Prins,et al.  Comparison of progression and non‐progression in injecting drug users and homosexual men with documented dates of HIV‐1 seroconversion , 1997, AIDS.

[30]  R. Brettle,et al.  Sudden death in HIV-infected drug users. Presumptive overdose in an HIV-positive narcotic addict. , 1993, The Journal of infection.

[31]  R. Elton,et al.  After the epidemic: follow up study of HIV seroprevalence and changing patterns of drug use. , 1990, BMJ.

[32]  J. Goedert,et al.  Mortality among drug users in the AIDS era. , 1995, International journal of epidemiology.

[33]  A. Kamali,et al.  Two-year HIV-1-associated mortality in a Ugandan rural population , 1994, The Lancet.