Page 252 - HIVMED_v21_i1.indb

Southern African Journal of HIV Medicine
ISSN: (Online) 2078-6751, (Print) 1608-9693
Page 1 of 2 Editorial

‘Covering the tail’ after stopping efavirenz-based

antiretroviral therapy

Single-dose nevirapine for the prevention of mother-to-child transmission (PMTCT) was
Author:
Gary Maartens 1 associated with the development of non-nucleoside reverse transcriptase inhibitor (NNRTI)
resistance mutations in a high proportion of women because of nevirapine’s low genetic barrier
Affiliation: to resistance. The hypothesis that dual nucleoside reverse transcriptase inhibitors (NRTIs) given
1 Division of Clinical
Pharmacology, Department for a short period to ‘cover the tail’ of slowly declining nevirapine concentrations would reduce
of Medicine, University of the risk of emergent NNRTI resistance mutations was borne out by two randomised controlled
Cape Town, Cape Town, trials of a single dose of tenofovir plus emtricitabine and 4–7 days of zidovudine plus lamivudine.
1,2
South Africa
Corresponding author: The practice of ‘covering the tail’ then migrated to stopping NNRTI-based combination
Gary Maartens, antiretroviral therapy (ART) started during pregnancy for PMTCT, which was ‘option B’ in World
[email protected]
Health Organization (WHO) guidelines for women who did not qualify for long term ART based
How to cite this article: on CD4 count thresholds. ‘Covering the tail’ was also recommended in guidelines, for all patients
Maartens G. `Covering the stopping NNRTI-based ART.
tail’ after stopping efavirenz-
based antiretroviral therapy.
S Afr J HIV Med. 2020;21(1), Is there evidence that ‘covering the tail’ after stopping NNRTI-based ART reduces the risk of
a1036. https://doi. developing NNRTI resistance, and is the practice relevant in the era of ART for all?
org/10.4102/sajhivmed.
v21i1.1036
In this edition of the journal, Ajibola et al. suggest that ‘covering the tail’ after stopping efavirenz-
3
Copyright: based ART might reduce the risk of developing NNRTI resistance (please see https://doi.
© 2020. The Authors. org/10.4102/sajhivmed.v21i1.1023). They conducted a retrospective study of women stopping
Licensee: AOSIS. This work efavirenz-based ART started in pregnancy as ‘option B’ in Botswana and found that women who
is licensed under the received a week of tenofovir plus emtricitabine after stopping ART had less NNRTI resistance.
Creative Commons
Attribution License. However, their study findings just failed to achieve statistical significance, likely because of the
small sample size. Another problem with the study is that allocation to ‘covering the tail’ was not
random. Because of these study limitations, we still lack good evidence that that ‘covering the tail’
after stopping NNRTI-based ART reduces the risk of developing NNRTI resistance.

The rationale for ‘covering the tail’ after stopping NNRTI-based ART is that efavirenz and
nevirapine have longer half-lives than the older NNRTIs. However, data from a pharmacokinetic
study question the need for ‘covering the tail’ with a regimen of tenofovir, emtricitabine and
efavirenz: the half-lives of intracellular tenofovir-diphosphate and emtricitabine-triphosphate
(the active drugs) is 164 and 39 h, respectively, compared with 92 h for plasma efavirenz. The
4
half-life of efavirenz is variable, largely explained by polymorphisms in CYP2B6, which encodes
the main metabolising enzyme: the prevalence of the CYP2B6 slow metaboliser genotype, which
5
results in a longer efavirenz half-life, is about 20% in South Africa. Therefore, in order to rationally
‘cover the tail’ after stopping efavirenz-based ART, the CYP2B6 metaboliser genotype should be
known and an additional dose or two of emtricitabine should be given; however, emtricitabine is
only available in the region co-formulated with tenofovir and genotype data are almost never
known. There is no good pharmacokinetic rationale for ‘covering the tail’ with a week of tenofovir
plus emtricitabine, which was recommended in the Botswana paper. Furthermore, the time to
viral rebound after stopping ART in patients who have achieved virologic suppression is variable,
but typically takes weeks rather than days and is longer with NNRTI-based ART. Finally, there
6
7
is rarely a medical indication to interrupt ART in the current era of ART for all. For these reasons,
the SA HIV Clinicians Society guidelines on ART no longer recommend ‘covering the tail’ if ART
is interrupted.
Read online:
Read online:
Scan this QR References
Scan this QR
code with your
code with your
smart phone or
smart phone or
mobile device 1. Chi BH, Sinkala M, Mbewe F, et al. Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse
mobile device
to read online. transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: An open-label randomised trial.
to read online.
Lancet. 2007;370(9600):1698–1705. https://doi.org/10.1016/S0140-6736(07)61605-5
http://www.sajhivmed.org.za 244 Open Access