Interrupting antiretroviral treatment needs particular care
BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7286.616 (Published 10 March 2001) Cite this as: BMJ 2001;322:616
- W A C Sewell, specialist registrar,
- C Mazhude, specialist registrar,
- A Murdin-Geretti, lecturer,
- S Jones, senior pharmacist,
- P J Easterbrook, professor (philippa.easterbrook{at}kcl.ac.uk)
- Academic Department of HIV/Genitourinary Medicine, Guy's, King's and St Thomas's School of Medicine, Weston Education Centre, London SE5 9RT
EDITOR—Noble and Kehlet raise an important issue in their editorial about the interruption of drug treatment during the postoperative period.1 We would emphasise the particular problems of drug interruptions in HIV infected patients receiving combination antiretroviral treatment; in these patients the general rule that some drugs are better than none does not apply.
Efavirenz and nevirapine are both non-nucleoside reverse transcriptase inhibitors with long plasma half lives (44-55 hours and 25–30 hours respectively) relative to the other main classes of antiretroviral drugs (nucleoside reverse transcriptase inhibitors (1-6 hours) and protease inhibitors (1-7 hours)).2 Thus if a patient is taking efavirenz or nevirapine as part of his or her HIV treatment in combination with two nucleoside reverse transcriptase inhibitors, and all the drugs are stopped at the same time, the long half lives of the inhibitors will result in a period of monotherapy with these agents perioperatively.
A similar situation may arise when antiretroviral drugs with dietary restrictions (for example, indinavir, nelfinavir, didanosine) are stopped earlier or restarted later in the perioperative period than other drugs in the regimen without such restrictions (for example, stavudine, lamivudine, zidovudine, nevirapine, efavirenz). HIV-1 has a rapid mutation rate, and so even brief periods of monotherapy may result in the rapid accumulation of drug resistant strains and loss of virological control (L Guay et al, seventh conference on retroviruses and opportunistic infections, San Francisco, 2000; abstract S12). This is a particular problem for antiretroviral drugs with a low genetic barrier (such as efavirenz, nevirapine, lamivudine), where a single mutation may result in phenotypic resistance.3
If possible, antiretroviral treatment should not be interrupted in patients undergoing general anaesthesia or other procedures for which they must be nil by mouth for a period. When an interruption is unavoidable all antiretroviral drugs should be stopped and restarted together, except for those with a long half life, which should be stopped two to four days before the others. We recommend that specialist HIV advice should be sought about antiretroviral management in individual patients.