Elsevier

The Lancet

Volume 362, Issue 9377, 5 July 2003, Pages 22-29
The Lancet

Articles
Decline in the AIDS and death rates in the EuroSIDA study: an observational study

https://doi.org/10.1016/S0140-6736(03)13802-0Get rights and content

Summary

Background

Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible changes in these rates across Europe.

Methods

We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6–monthly periods and in three treatment eras (pre-HAART, 1994–1995; early-HAART, 1996–1997; and late-HAART, 1998–2002).

Findings

The incidence of AIDS or death fell after September, 1998, by 8% per 6–month period (rate ratio 0·92, 95% CI 0·88–0·95, p<0·0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/μL or less (0·43, 0·35–0·53, p<0·0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0·0001). In multivariate Cox's models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1–39; 95% CI 1–16–1–67, p=0·0004) and all deaths (1–29; 1–08–1–56, p=0·0065) in the pre-HAART era, and a reduced risk of AIDS (0·62; 0·50–0–77, p<0·0001) and all deaths (0·66; 0·53–0·82, p=0·0002) in the late-HAART era.

Interpretation

The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.

Introduction

The introduction of highly active antiretroviral therapy (HAART) during 1996 and 1997 led to a well-documented reduction in mortality and risk of AIDS-defining illnesses.1, 2, 3, 4 The death rate across Europe dropped rapidly, and within 2 years of the widespread availability of HAART,5 the number of deaths were less than a fifth of those before HAART.1 The initial success associated with HAART might not have continued, and high levels of treatment failure have been reported,6, 7, 8 which has been associated with serious adverse events, emergence of drug resistance, difficulties in maintenance of long-term adherence, and the few types of drugs available.9, 10

The EuroSIDA study was started in 1994 and provides an ideal opportunity to follow a large cohort of patients to describe patterns of mortality and morbidity in the era of HAART. The aims of this study were to examine changes in AIDS and death rates during this time.

Section snippets

Patients

The EuroSIDA study is a prospective study of patients with HIV-1 in 70 centres across Europe, and now includes Argentina and Israel.11 The centres provided data for consecutive patients seen in outpatient clinics from May, 1994, until a predefined number of patients was enrolled from each centre. To be eligible for inclusion, patients needed to have a prebooked clinic appointment and be aged over 16. The EuroSIDA I cohort was the first 3116 patients enrolled. The second cohort (n=1365) was

Statistical methods

Three treatment periods were defined before the study; the pre-HAART era (1994–1995), early-HAART (1996–1997), and late-HAART (1998 onwards). The characteristics of patients were analysed separately according to the treatment era in which they were recruited. To calculate event rates, we used 6–month intervals using the same calendar periods and methodology as described previously.1 The incidence of AIDS or death was calculated as the number of events per person-years of follow-up (PYFU) for

Role of the funding source

The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Results

Table 1 shows characteristics of the patients grouped according to whether they were enrolled pre-HAART, early-HAART, or late-HAART. As expected, demographic characteristics of patients in the various treatment eras differed greatly. The proportion of intravenous drug users enrolled fell over time, from 26·8% in the pre-HAART era to 22·9% in late-HAART (p<0·0001). Because of the study design, no patients were enrolled from Eastern Europe or Argentina until the late-HAART era. Patients recruited

Discussion

The results of this study with over 30 000 PYFU show that the combined incidence of AIDS and death has continued to fall in the later years of HAART. Although changes in CD4 counts could account for most of the differences in relative risk of death in different treatment eras, they did not explain the differences in the relative risk of AIDS.

Since the initial fall in AIDS and death rates associated with the introduction of HAART,1, 2, 3, 4 few studies have a longitudinal follow-up over several

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