The objective of this study was to estimate the cumulative
incidences of failure by months 12 (M12) and 24 (M24) for the most prescribed
first-line anti-retroviral regimens (ART).
It is retrospective analysis of a prospectively
collected database.
All patients who initiated their first ART with the
most prescribed regimens between 1st January 2004 and 30th June 2013 in 12
large HIV reference centers in France were included. The outcome was treatment
failure—defined by any treatment modification for virological or tolerability
reasons—and comparisons between regimens were carried out at M12 and M24.
Adjusted and weighted methods via the propensity score (PS) were used to
compare the effectiveness of the first antiretroviral regimens. Potential
confounders of the treatment-outcome association were used to estimate PS with
multinomial logistic regression.
Overall, 3128 and 2690 patients were included in
the M12 and M24 analyses, respectively. Patients received 5 different regimens
(ABC/3TC with ATV/r or DRV/r, TDF/FTC with ATV/r, DRV/r, or EFV). Failure was
reported in 25% and 42% at M12 and M24, respectively. Patients who received
TDF/FTC/EFV had a significantly higher proportion of failure at M12 by
comparison with TDF/FTC with DRV/r (reference), but not at M24. Patients in the
3 other groups had a trend toward a higher proportion of failure at M12
although not statistically significant. No difference was found at M24.
Using data from a large prospective cohort, we
found that boosted atazanavir and darunavir had comparable effectiveness,
whatever the associated NRTIs, whereas efavirenz-based regimens were relatively
less performing on the short term...
We here provide a comparison of the effectiveness of the 5
most prescribed first-line ART regimens for HIV-infected patients in France
between 2004 and 2013. The 2 most frequently used regimens were TDF/FTC with
either EFV or DRV/r as recommended in international HIV treatment guidelines.1–3 ABC/3TC with ATV/r was
received by >300 patients although it was not a recommended regimen. By July
2013, the number of patients receiving INSTI-based regimens (not recommended as
first-line in France before 2014) was not large enough to be included in the
present analysis. Crude treatment failure rates at months 12 and 24 were 25 and
42%, respectively. Patients receiving TDF/FTC with DRV/r had the lowest risk of
treatment failure at months 12 and 24. After controlling for confounding by
propensity score modeling, marginal structural models and double robust we
found that, at month 12, patients receiving TDF/FTC with EFV had a significantly
higher probability of treatment failure. Patients receiving boosted atazanavir
regimens and ABC/3TC with DRV/r had a nonsignificantly higher probability of
treatment failure. At month 24, all regimens had a comparable effectiveness.
The observed crude failure rate, ∼25% at 1
year, is in line with the finding that 47% of the patients of our cohort
changed their first-line regimen before the end of the first year, whatever the
reasons for treatment modification.18 Thus, it is a reasonable
estimation of treatment effectiveness. By comparison, the 1 and 2-year
cumulative incidences of treatment modification in patients initiating ART in
2002 to 2009 were 25 and 39%, respectively, in a large collaboration of cohort
studies.19 As observed in RCTs,
treatment modifications were mainly due to adverse events rather than to
virological or clinical failures. Fifty percent of failing patients modified
their regimen during the first 3 months. Early interruption of ART regimens due
to short-term poor tolerability has already been described.19,20
Observational studies provide an insight in how different
treatments will be used in “real life” by the patients and their physicians. We
studied a large population seeking care in different centers, representative of
the patients under care in France during the last 10 years. The large
population of our cohort fulfills the necessary condition to allow the
selection of regimens for which no data have been produced by RCTs.21 Permanent assessment and
control of the quality of the database15 limits the errors that
one can encounter with this type of studies. Appropriate analysis of carefully
collected prospective observational data can then complement the findings of
RCTs22 to avoid that first-line
regimens be chosen by the physicians on the basis of self-conviction, indirect
comparisons, or other factors.
By choosing a pragmatic definition of treatment failure, we
took into account some reasons for failure that may not be accounted for in
RCTs. Most trials used virological failure as primary endpoints, but treatment
modifications should also be considered as failures. The large number of
planned visits in an RCT, especially during the first year, and strict protocol
rules are 2 important differences with observational studies. One can suspect
that clinicians modified patients’ regimen more easily and early in clinical
practice than in an RCT. The surprisingly high probability of failure rate in
the most recent calendar years can be explained by the availability of an
increasing number of potent drugs leading to treatment modifications for minor
toxicities. Comparative effectiveness of initial antiretroviral therapy
regimens based on virological failure between RCTs and observational studies
have been made and showed a good agreement...23
By:
From the INSERM,
UMR 1027, Toulouse, France; Université de Toulouse III, Toulouse, France; CHU
Toulouse, COREVIH Toulouse, France (LC); Infectious Diseases Dpt, CHU Archet,
Nice, France (PP); Infectious Diseases Dpt, CHU Hotel Dieu, Nantes, France
(CA); Sorbonne University UPMC Univ Paris 06-UMR_S 1136 Pierre Louis Institute
of Epidemiology and Public Health; AP-HP, Groupe hospitalier Pitié Salpêtrière,
Service des Maladies Infectieuses, Paris, France (CK); Infectious Diseases Dpt,
Hospices Civils de Lyon, Lyon, France and INSERM U1052, Lyon, France (LC);
Université Paris-Descartes, Sorbonne Paris Cité, Paris, Infectious Diseses Dpt,
Tourcoing, France (AC); Infectious Diseases Dpt, and Université Antilles
Guyane, CHU de Martinique, France (AC); Le Trait d’Union, HIV care center, CHU
Strasbourg, France (DR); UMR CNRS 6249 Chrono-Environnement, Université de
Franche-Comté; Service de maladies infectieuses, CHRU Besançon, France (CC);
Reims Champagne-Ardenne University, Faculté de médecine, EA-4684/ SFR
CAP-SANTE; CHU Reims, Hôpital Robert Debré, Tropical and Infectious Diseases,
Reims, France (FB-S); and INSERM, UMR-S 1136 and Sorbonne Universities, UPMC
University Paris 06, Pierre Louis Institute of Epidemiology and Public Health,
Paris, France (PF).
Correspondence: L Cuzin, COREVIH, Batiment Turiaf, Hopital
Purpan, TSA40031, Toulouse cedex, France (e-mail: rf.esuoluot-uhc@l.nizuc).
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