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.
Prins
M
M
Municipal Health Service, Division of Public Health and Environment, Amsterdam, The Netherlands.
Brettle
R P
RP
Robertson
J R
JR
Hernández Aguado
I
I
Broers
B
B
Carré
N
N
Goldberg
D J
DJ
Zangerle
R
R
Coutinho
R A
RA
van den Hoek
A
A
D000328:Adult; D018791:CD4 Lymphocyte Count; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000635:transmission*; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D015819:Substance Abuse, Intravenous / Q000276:immunology