Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis

Summary

Background

We used data from Europe, North America, and Australia to assess the effect of exposure category on the AIDS incubation period and HIV-1 survival and whether the effect of age at seroconversion varies with exposure category and with time since seroconversion.

Methods

38 studies of HIV-1-infected individuals whose dates of seroconversion could be reliably estimated were included in the analysis. Individual data on 13 030 HIV-1-infected individuals from 15 countries were collated, checked, and analysed centrally. We calculated estimates of mortality and AIDS incidence rates and estimated the proportions of individuals surviving and developing AIDS at each year after seroconversion from the numbers of observed deaths or cases of AIDS and the corresponding person-years at risk. Analyses were adjusted for age at seroconversion, time since seroconversion, and other factors as appropriate.

Findings

Mortality and AIDS incidence increased strongly with time since seroconversion and age at seroconversion. Median survival varied from 12·5 years (95% Cl 12·1–12·9) for those aged 15–24 years at seroconversion to 7·9 years (7·4–8·5) for those aged 45–54 years at seroconversion, whereas for development of AIDS the corresponding values were 11·0 years (10·7–11·7) and 7·7 years (7·1–8·6). There was no appreciable effect of exposure category on survival. For AIDS incidence, the exposure category effect that we noted was explained by the high incidence of Kaposi's sarcoma in those infected through sex between men. We estimated that among people aged 25–29 years at seroconversion 90% (89–91) and 60% (57–62) survived to 5 years and 10 years, respectively, after seroconversion, whereas 13% (12–15) and 46% (44–49), respectively, developed AIDS (excluding Kaposi's sarcoma).

Interpretation

Before widespread use of highly-active antiretroviral therapy (before 1996), time since seroconversion and age at seroconversion were the major determinants of survival and development of AIDS in Europe, North America, and Australia.

Introduction

Reliable estimates of AIDS incubation period, survival time after HIV-1 seroconversion, and factors that influence them are essential to enable us to understand the natural history of HIV-1 disease and to plan healthcare resources. Follow-up studies of HIV-1-infected individuals whose dates of seroconversion can be estimated with reasonable accuracy have been the major source of information for these estimates to date.

Much has already been learnt about the determinants of HIV-1 disease progression. Age at seroconversion is recognised as a crucial factor, with younger age being predictive of slower progression.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 Also, the route through which infection is acquired might affect the rate of disease progression.12, 13, 14 However, differences between cohort studies in their methods and the range of ages at seroconversion and exposure group of their participants have prevented a full understanding of such effects, leading to apparent inconsistencies. Several specific questions remain unanswered. Does age at seroconversion predict HIV-1 disease progression in all exposure categories? Is the effect of age equally strong in the different exposure categories? After controlling for age at seroconversion, does the mode through which infection is acquired affect the rate of disease progression or mortality? Is the effect of age at seroconversion quantitatively similar throughout the whole period after seroconversion?

We report an international collaboration established to bring together data from all seroconverter cohorts in Europe, North America, and Australia. The main objective was to provide accurate estimates based on all available data of the time from HIV-1 seroconversion to AIDS and death for people infected at different ages, in different periods, and in different ways, while controlling for the effects of other factors and accounting for differences in methods where appropriate and possible. We report the analyses done to assess the effect of age at seroconversion and exposure category on HIV-1 progression before the advent of highly-active antiretroviral therapy. Additional information, including details of the methods of data collection and the effects of other covariates, will be given elsewhere.