CHAIN: Collaborative HIV and Anti-HIV Drug Resistance
CHAIN is a large scale integrating
project aimed at effectively and durably combating new and existing
anti-HIV drug resistance in clinical settings, with a special
emphasis on Eastern Europe and heavily affected resource-poor
regions in Africa.
A joint project on transmitted drug resistance
(TDR) and its impact on treatment response between EuroCoord and
the EU funded FP7 CHAIN was instigated due to the large number of
patients required to address the scientific question.
The objective was to compare virological,
immunological, and clinical outcome up to 12-16 months following
initiation of cART, according to markers of virus variability
(specific mutations, subtypes), and relevant to the drugs in the
regimen (objective 3.4 of CHAIN WP3 entitled ‘Clinical implications
of HIV drug resistance’). A project team with epidemiologists,
statisticians, virologists, and clinicians was established (project
lead: Geneviève Chêne, project coordinator: Linda Wittkop).
The Standardised Operating Procedure (SOP) in
HICDEP format used
for COHERE data mergers was improved and
adapted for this joint project to involve other founding networks
of EuroCoord: CASCADE, EUROSIDA, and PENTA.
Data collection started in April 2009 (all
HIV-1 infected patients with at least one genotypic resistance test
while antiretroviral naive and with minimal core data available as
described in the SOP) and the last cohort submitted data in
A total of 10,056 patients from 25 cohorts were included in the
final analysis which was published in Lancet Infectious Diseases.
The study found that TDR was associated with virological failure in
patients who received at least one drug to which the virus had lost
susceptibility. The group also found that treatment with a drug
classified even with low-level resistance is associated with a
significantly higher risk for virological, emphasising the need for
at least three fully-active drugs in a first-line regimen.
A further finding of the study showed that patients with TDR who
started a regimen containing two NRTIs plus one ritonavir-boosted
protease inhibitor and received fully-active treatment had a
similar risk of virological failure to patients with a virus with
no TDR mutations. Therefore, if drug resistance mutations are
detected before treatment initiation, a ritonavir-boosted protease
inhibitor can be included in the first treatment regimen, which,
because of its higher genetic barrier, could better protect from
the risk of virological failure than could NNRTI.
Further proposals have been made to use the
dataset, and they are currently undergoing review.
Wittkop L, Günthard H, de Wolf F, Dunn D, Cozzi-Lepri A, de
Luca A, Kücherer C, Obel N, von Wyl V, Masquelier B, Stephan C,
Torti C, Antinori A, García F, Judd A, Porter K, Thiébaut R, Castro
H, van Sighem AI, Colin C, Kjaer J, Lundgren JD, Paredes R, Pozniak
A, Clotet B, Phillips A, Pillay D, Chêne G, for the EuroCoord-CHAIN
study group. Effect of transmitted drug resistance on virological
and immunological response to initial combination antiretroviral
therapy for HIV (EuroCoord-CHAIN joint project): a European
multicohort study. Lancet Infect. Dis. 2011. [Epub ahead of
For more information, visit
the CHAIN website