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Risk of NNRTI resistance following abrupt cessation of NNRTI-based HAART: implications for Haiti

By Chris Behrens | 04 Feb, 2010 Last edited by Anat Rosenthal, PhD on 12 May 2010

Greetings - the recent earthquake in Haiti will likely result in many
HIV-infected patients losing access to ARVs due to migration, facility
closures & stockouts, etc. The vast majority of patients on HAART in Haiti
are on NNRTI-based regimens (EFV or NVP). For such patients who have to
interrupt their HAART regimens for a prolonged period of time (say, one
month), what is the risk that clinically significant NNRTI resistance will
develop?

>From my brief review of the literature, the Structured Treatment
Interruptions (STI) data suggest that this is a real risk, which makes sense
given the long half-life of NNRTIs compared with the NRTIs (such that abrupt
cessation of HAART can result essentially in NNRTI monotherapy for 1-3
weeks). However, I have not been able to find an estimate of how high the
risk is. Furthermore, the STI data tend to examine rates of resistance in
patients who have undergone multiple treatment interruptions.

In forecasting the future need for 2nd line agents in Haiti, it would help
to have some idea regarding what % of patients who are forced to abruptly
discontinue NNRTI-based HAART will likely require 2nd line ART due to the
evolution of resistance.

Thanks for any input you may have -
Chris

=========================================================
Chris Behrens, MD
Clinical Assistant Professor of Medicine, University of Washington
Medical Director, International Training & Education Center on Health
www.go2itech.org
=========================================================
I-TECH is a global network that supports the development of a skilled health
work force and well-organized national health delivery systems in order to
provide effective prevention, care, and treatment of infectious disease in
the developing world.

Replies

 

Jessica Haberer, MD, MS Replied at 10:54 AM, 8 Feb 2010

Hi Chris,

I think you might find this article useful:

Two-months-off, four-months-on antiretroviral regimen increases the risk of resistance, compared with continuous therapy: a randomized trial involving West African adults (Danel, J Infect Dis. 2009 Jan 1;199(1):66-76).

Xavier Anglaret (one of the authors) told me: "See the discussion:
"Because of the randomized trial design, to our knowledge our data provide the first accurate estimate of the additional risk of
resistance associated with each new interruption of efavirenz in African adults. At 24 months, after 4 cycles of interruptionreintroduction,
the difference in resistance to efavirenz between arms was 20% and was about twice as high as the difference at 12
months, after 2 cycles. Thus, the additional risk at each new efavirenz interruption was close to 5%."

Just a comment: this 5% risk was with a 5-day NRTI covering period. Thus, with a 0-day period the risk would be higher, and 5% should be seen a a lower bound for the estimate of the risk.


I hope this is helpful.

Best,
Jessica

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