Page 48 - HIVMED_v21_i1.indb

Page 22 of 39 Guideline

Exceptions • Maraviroc (a CCR5 blocker) is a consideration in third-
There are exceptions: line therapy; however, it is currently extremely costly and
can only be used after a tropism test demonstrates that
• In patients with renal impairment, replace TDF + FTC with the patient’s circulating virus has sole tropism for the
ABC + 3TC, or AZT + 3TC. The choice between ABC and CCR5 co-receptor. We advise only considering this when
AZT will depend on Hb (anaemia: do not use AZT if Hb < there is intermediate- or high-level resistance to all PIs, all
8 g/dL) and resistance testing. NNRTIs and all NRTIs, and DTG is not fully susceptible.
• If the AZT Stanford score is lower than the TDF score, • If viral suppression is not achieved on third-line therapy,
then use AZT + 3TC rather than TDF + FTC. then there is still benefit in continuing failing ART because
• Patients with a DRV score of 0 on Stanford score (and of the residual partial activity and ‘crippling’ effect of
no DRV mutations, see section 5) can take DRV/r such ART. ‘Crippling’ describes the fact that mutant
800 mg/100 mg once daily. viruses often have less replicative capacity. Provided that
• Patients with prior virological failure on RAL and/or the VL can be maintained at < 10 000 copies/mL, the
with a DTG score > 0 on integrase resistance testing CD4 count will usually be maintained or even increase. 59
+
should receive DTG 50 mg twice daily.
• In patients with extensive resistance (e.g. DRV score > 29 Third-line regimen choice after failing a
and NRTI score > 29), consider adding RPV or ETR dolutegravir-based second-line regimen
(provided that the score for these drugs is < 30) or
maraviroc (MVC) (provided that the virus is CCR5-tropic The choice of a regimen will be guided by resistance test
on the tropism test). results and should include DRV/r with two NRTIs (generally
3TC or FTC with the NRTI with the lowest Stanford score). In
Additional points and explanatory notes patients failing a second-line DTG regimen who have not
failed a PI/r previously, it can be assumed that DRV/r is fully
• We generally advise the continuation of NRTIs in the active and can be used at 800 mg/100 mg daily. Based on the
third-line regimen, even if there is documented NRTI results of the EARNEST, SELECT and SECOND LINE trials,
resistance. it can be concluded that a DRV/r regimen with two NRTIs
• Lamivudine (or FTC) resistance with the M184V mutation will be an active regimen even if there is documented
impairs viral replication. Another NRTI (generally TDF, resistance to the two NRTIs. 60,61,72 However, decisions
but based on resistance testing) should be added. This is regarding the third-line therapy need to be individualised in
not essential if there are more than two other active drugs consultation with an expert, taking into account the treatment
in the regimen. 78 history (which drugs and classes the patient previously
• Because most patients are not receiving an NNRTI at the failed) and previous and current resistance test results.
time of failing second-line therapy when a genotype
resistance test is typically performed, prior NNRTI Raltegravir may still be active in patients with DTG
mutations related to first-line NNRTI failure may be resistance – it depends on the specific resistance mutations
archived at this time. Therefore, it is difficult to be certain in the integrase gene – but it is usually not necessary to
from a (this) genotype performed at second-line ART include it in the regimen. Etravirine and RPV are other drugs
failure whether ETR/RPV is still active; however, data that can be considered depending on resistance test results
from South Africa suggest that the majority of patients who and treatment history.
have failed NVP or EFV are still susceptible to ETR/RPV.
79
• In the SAILING trial, in treatment-experienced patients, a 15. Laboratory monitoring of the
DTG regimen proved superior to RAL and fewer patients
in the DTG arm developed treatment-emergent InSTI efficacy and safety of
resistance. Consequently, we no longer recommend the use of antiretroviral therapy
RAL in third-line therapy unless DTG is not tolerated or Key points
otherwise contraindicated or unavailable. We also recommend
switching patients currently using RAL in third-line ÿ Antiretroviral therapy efficacy is monitored with VL and
therapy to DTG because of its higher barrier to resistance. CD4 count – discussed in the sections ‘Viral load’ and
14
+
If such patients have a suppressed VL, then they can be ‘CD4 cell count’.
+
switched to standard dose DTG (50 mg daily); however, if ÿ The key efficacy endpoint in ART is sustained virological
they are not virologically suppressed, then we suggest a suppression with a VL < 50 copies/mL.
resistance test with a request for integrase sequencing ÿ CD4 count monitoring can be stopped when the CD4
+
+
before switching. If there are InSTI mutations present that count is > 200 cells/μL and the VL is suppressed.
are associated with reduced susceptibility to DTG, then ÿ Creatinine monitoring is advised in patients on TDF, and
the DTG dose should be 50 mg twice daily. an FBC is advised in patients on AZT.
• Women of childbearing potential should be counselled ÿ In most patients taking PIs, only one lipid measurement
about the risk and benefits of DTG and allowed to make is advised (at 3 months).
an informed decision regarding the use of DTG and ÿ In patients on TDF who are admitted to hospital, it is
contraception. important to check creatinine even if it does not fall

http://www.sajhivmed.org.za 40 Open Access