The overall aim of this project is to study the virological characteristics of
new HIV-1 infections from around Europe. The project will focus on the HIV-1
subtypes, which are a reflection of the worldwide geographical origin of
infections, and the presence of drug resistant strains, which, if present in
primary infection, represent transmission of drug resistant virus. A number of
cohorts of persons with known dates of HIV seroconversion (seroconverters)
enrolled within the CASCADE will be utilised.
CASCADE has described the lack of change in the AIDS incubation period and
survival in Europe prior to the introduction of potent anti-retroviral therapy
combinations in the mid-1990s. The clinical course of HIV disease has improved
dramatically since the introduction of highly active anti-retroviral therapy
(HAART) and CASCADE has been able to quantify such change by providing estimates
of the current survival expectations. However, the number of new infections
within Europe continues to rise. The unfolding of the epidemic during this
period has been characterised by two key virological parameters, which have
potential bearing on the incubation period and survival in seroconverter
cohorts. Firstly, the emergence of drug resistance in treated individuals has
led to the transmission of resistant virus strains. Secondly, the ongoing
migratory patterns into,and within Europe has been associated with the
introduction of a wider variety of HIV-1 subtypes then had previously existed.
One of the main characteristics of HIV is its extensive genetic diversity. The
major group circulating globally is M, which can be divided into a number of
subtypes, based on genomic relatedness. These subtypes (A-K), as well as 11
recombinant forms, are geographically distributed, and therefore represent a
marker of migration. It is expected that these diverse viruses will be further
spread within Europe by the ongoing epidemic.
The aims of this project are:
1) to estimate the association between the pattern of genotypic resistance
and virological, immunological and clinical outcome
2) to estimate to what extent, if any, infection with drug resistant HIV
affects response to first-line therapy
3) to examine differences in HIV RNA levels in persons infected with
different HIV subtypes who have similar CD4 levels
4) to examine changes in the prevalence of HIV drug resistance in primary
infection over time
5) to examine factors associated with differences in primary resistance
prevalence estimates, such as age; exposure category, sex and country of
6) to examine the evolution of key mutations over time in the absence of
1) Report on the association between infection with drug resistant HIV and
response to first-line therapy.
2) Report on the association between the initial pattern of genotypic
resistance and virological,
immunological and clinical outcome.
3) Report on differences in HIV RNA in persons infected with different HIV
subtypes with similar CD4 levels.
4) Report on changes in the prevalence of HIV drug resistance in primary
5) Report on factors associated with transmitted resistance mutations.
6) Report on evolution of key mutations detected at the time of
seroconversion in treated and untreated persons.
7) Compile a high quality pooled dataset of data on transmitted drug
resistant HIV, HIV subtype and epidemiolgic and clinical data on persons with
known dates of HIV seroconversion.
Data arising from this study will be crucial to assessing whether HIV-1 drug
resistance testing should be undertaken in primary infection alone, or in all
new HIV-1 diagnoses. Such information will allow for more individualised
HIV-1 therapy at the initiation of treatment.
Results will help reinforce the public health messages regarding the
importance of safe sex in preventing the spread of drug resistant HIV-1 and in
providing an epidemiological basis for decisions on the allocation of HIV
prevention resources to new migrant communities within Europe.