Partially
Active NRTIs Can Improve Response to Raltegravir for Salvage
Therapy
By
Liz Highleyman
Salvage
therapy refers to treatment for people who have used and developed
resistance to most available antiretroviral
drugs. Often this happens due to suboptimal use of drugs
as monotherapy or dual therapy before the advent of effective
combination antiretroviral
therapy (ART).
Genotypic testing typically reveals that such patients have
HIV with mutations conferring
full or partial resistance to NRTIs.
This raises the question of whether to stay on these supposedly
ineffective drugs, or to drop them in an effort to reduce
side effects, cost, and inconvenience.
To explore this issue, Alexandra Scherrer from the University
of Zurich and fellow investigators with the Swiss HIV Cohort
Study compared the efficacy of antiretroviral regimens containing
the recently approved integrase inhibitor raltegravir
plus either 2 NRTIs -- as recommended in current
treatment guidelines -- or 0 or 1 NRTI.
The analysis included 130 HIV positive Swiss cohort participants.
The researchers evaluated viral suppression (HIV RNA <
50 copies/mL) after 24 weeks. This was an observational study
looking at real world clinical practice; participants were
not randomly assigned to take 2 or less than 2 NRTIs, allowing
for the possibility that there were other differences between
the groups that might have influenced the results.
Results
 |
More
than half (58.5%) of participants were taking less than
2 NRTIs. |
|
Discontinued
NRTIs were often replaced with other drug classes. |
|
Patients
taking 2 NRTIs received fewer additional drug classes
than those taking 1 or no NRTIs. |
|
Non-NRTI
components of a regimen were significantly less active,
on average, among people taking 2 NRTIs (median genotypic
sensitivity score of 2.0 vs 2.5, respectively). |
|
Using
fewer than 2 NRTIs was associated with a significantly
lower rate of virological response at week 24. |
|
This
remained the case even when genotypic testing indicated
partial or full NRTI resistance. |
These
results led the investigators to conclude, "Our findings
showed that partially active or inactive NRTIs contribute
to treatment response, and thus the use of 2 NRTIs in salvage
regimens that include raltegravir seems warranted."
Investigator affiliations: Division of Infectious Diseases
and Hospital Epidemiology, University Hospital Zürich,
University of Zürich; Institute of Medical Virology,
Swiss National Center for Retroviruses, University of Zürich;
Central Laboratory of Virology and Division of Infectious
Diseases, Geneva University Hospital; Institute for Medical
Microbiology, University of Basel; Division of Immunology
& Allergy and Infectious Diseases Service, University
Hospital Lausanne; Division of Infectious Diseases, University
Hospital Berne; Division of Infectious Diseases and Hospital
Epidemiology, University Hospital Basel; Division of Infectious
Diseases, Cantonal Hospital St. Gallen; Regional Hospital
Lugano, Switzerland.
2/25/11
Reference
AU
Scherrer, V von Wyl, J Boni, and others. Viral suppression
rates in salvage treatment with raltegravir improved with
the administration of genotypic partially active or inactive
nucleoside/tide reverse transcriptase inhibitors. Journal
of Acquired Immune Deficiency Syndromes (abstract).
January 28, 2011.
