Elsevier

The Lancet

Volume 360, Issue 9327, 13 July 2002, Pages 119-129
The Lancet

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Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies*

https://doi.org/10.1016/S0140-6736(02)09411-4Get rights and content

Summary

Background

Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap.

Methods

We analysed data on 12 574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group.

Findings

During 24 310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/μL, adjusted hazard ratios were 0·74 (95% CI 0·62–0·89) for 50–99 cells/μL, 0·52 (0·44–0·63) for 100–199 cells/μL, 0·24 (0·20–0·30) for 200–349 cells/μL, and 0·18 (0·14–0·22) for 350 or more CD4 cells/μL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100 000 copies/mL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3·4% (2·8–4·1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43–58) in patients in the highest-risk strata.

Interpretation

The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines.

Introduction

The widespread use since 1996 of highly active antiretroviral therapy (HAART)—a combination of at least three drugs that typically includes either a protease inhibitor (PI) or a non-nucleoside-analogue reverse-transcriptase inhibitor (NNRTI) and two nucleoside-analogue reverse-transcriptase inhibitors (NRTIs)—has substantially improved the prognosis of HIV-1-infected patients.1, 2, 3 However, accurate estimates of the probability of clinical progression in treatment-naive men and women of different ages and exposure categories, according to different levels of immunodeficiency and viral replication, are not available at present. Information on prognosis is of obvious importance to patients and is also required to gain a better understanding of the treated history of HIV-1 infection, to develop treatment guidelines, to monitor and predict the progress of the HIV/AIDS epidemic, and to plan health services in the era of HAART. Such data are also important as a basis for comparisons with treatment outcomes in resource-poor settings, once HAART becomes more widely available in less developed countries.4

The analysis by Mellors and colleagues5 of homosexual men enrolled in the Multicenter AIDS Cohort Study (MACS) who had frozen plasma samples on which HIV-1 RNA concentration (viral load) could be measured was influential in defining prognosis according to levels of viral load and CD4 cell count in the pre-HAART era. The Collaborative Group on AIDS Incubation and Survival provided precise estimates of the time from HIV-1 seroconversion to AIDS and death according to age at seroconversion and exposure category before the advent of HAART.6 In these studies, a large proportion of patients developed AIDS during extended periods of follow-up. In the era of HAART, the relatively small number of patients who experience clinical progression on therapy, and the limited length of follow-up since HAART became widely used, mean that the statistical power to define prognosis is limited even in large prospective studies. At present, no single cohort study can provide accurate estimates of progression to AIDS or death from initiation of HAART for treatment-naive patients at different levels of risk. Numerous analyses of trials and observational databases have focused on the increase in CD4 cell counts and virological response after commencing HAART, but these are imperfect surrogate endpoints for clinical progression.7, 8

We report the results from the Antiretroviral Therapy (ART) Cohort Collaboration—an international collaboration between the investigators of 13 cohort studies from Europe and North America that was established to bring together a large body of data on clinical progression in treatment-naive patients starting HAART.

Section snippets

Eligibility of cohorts and patients

Prospective cohort studies were eligible if they had enrolled at least 100 patients with HIV-1 infection aged 16 years or older who had not previously received antiretroviral treatment (treatment-naive) and who had started antiretroviral therapy with a combination of at least three drugs, including NRTIs, PIs, and NNRTIs, with a median duration of follow-up of at least 1 year. One CD4 T-cell count (CD4 count) and one measurement of viral load 0–3 months before starting therapy were also

Results

The characteristics of the 13 participating cohorts are shown in table 1. Ten cohorts were from European countries, including the multicentre EuroSIDA study, two from Canada, and one from the USA. The number of study centres ranged from one to 68, the number of patients included in the present analysis from 92 to 4739.

12 574 patients met our inclusion criteria. The median calendar month of starting HAART was December, 1997 (IQR June, 1997, to July, 1998). The characteristics at the time of

Discussion

The results of this collaborative study, involving 13 prospective studies and over 12 000 HIV-1-infected patients, showed that the prognosis of HIV-1 infection in patients starting HAART could be estimated with precision for groups of patients characterised by different levels of CD4 count, plasma viral load, and other prognostic factors. Because all patients were treatment-naive, our results are not confounded by previous antiretroviral therapy, and are relevant to most patients starting HAART

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    *

    Members of the study groups who made this collaboration possible are listed at end of paper

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