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Page 17 of 39 Guideline

TABLE 12: Alternative initial antiretroviral therapy regimens for previously ÿ The typical criteria of two VL measurements greater than
untreated patients. a certain threshold are not appropriate for DTG-based
Regimen Notes
TDF + 3TC (or FTC) + • EFV can be used at 600 mg nocte or 400 mg nocte. regimens, despite an adherence intervention to define
EFV • EFV 400 mg dose is associated with fewer side effects and virological failure. Rather, in patients started on a first-
less LTFU. 22
• EFV 400 mg dose is not available in FDC in South Africa. line DTG regimen, we recommend switching to a second-
• There are insufficient data to recommend the EFV 400 mg line therapy only if there is demonstrated InSTI resistance.
dose in patients who are pregnant and patients receiving
RIF although small-cohort studies have suggested that
adequate concentrations are achieved in these patients. 65,66 Patients currently on an efavirenz-, rilpivirine-
TDF + 3TC (or FTC) + • RPV cannot be used in patients receiving RIF.
RPV • RPV should not be used in initial therapy when baseline VL or nevirapine-based first-line regimen
is > 100 000 copies/mL.
ABC + 3TC + DTG • International guidelines recommend HLA-B*5701 testing Patients on these treatment regimens should have VL
before prescribing ABC because a negative result rules out measurements performed 6–12 monthly (see the sections
the risk of hypersensitivity reaction. However, this
genotype is very rare in people of African descent and is ‘Viral load’ and ‘Laboratory monitoring of the efficacy and
thus probably not indicated.
• In patients of non-African descent, HLA-B*5701 testing safety of antiretroviral therapy’). Given that DTG is now
should be considered if ABC is to be used, although access
to this test is limited in South Africa. readily available, clinicians can consider switching patients
3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; LTFU, who are known to have virological suppression (VL < 50
loss to follow-up; RIF, rifampicin; RPV, rilpivirine; TDF, tenofovir; VL, viral load; FDC, fixed- copies/mL within last 6 months) from EFV (or NVP or RPV)
dose combination.
to DTG whilst maintaining the same two-drug NRTI backbone.
TABLE 13: Recommended alternative initial antiretroviral therapy regimens in If the patient is tolerating the EFV (or RPV or NVP) regimen
specific clinical situations where TDF + 3TC (or FTC) + DTG cannot be used. with no side effects, then such a switch is optional, as the
Scenario Alternative regimen patient may develop DTG-related side effects which he or she
Renal impairment at baseline (CrCl ABC + 3TC + DTG†
< 50 mL/min) was not experiencing on the NNRTI (e.g. insomnia and weight
Renal impairment develops on TDF ABC + 3TC + DTG gain). The benefit of such a switch is that a DTG regimen has a
Patient is intolerant of DTG side TDF + 3TC (or FTC) + EFV (or RPV) more robust resistance profile (DTG boasts a higher barrier to
effects 12
Pure red cell aplasia develops TDF + DTG (can then add AZT when Hb has resistance than NNRTIs). An additional benefit of switching
because of 3TC/FTC recovered) from NVP to DTG is that it is switching from a twice-daily to a
(or RPV + DTG, provided that VL is suppressed)
once-daily regimen. In patients experiencing EFV-related side
3TC, lamivudine; ABC, abacavir; AZT, zidovudine; CrCl, creatinine clearance rate; DTG,
dolutegravir; EFV, efavirenz; FTC, emtricitabine; Hb, haemoglobin; RPV, rilpivirine; TDF, effects (even mild side effects), we encourage a change to DTG
tenofovir; VL, viral load. whilst maintaining the same NRTIs, provided that the VL is
†, In such patients, if renal function subsequently improves (CrCl > 50 mL/min), then they can
be switched to TDF + 3TC + DTG. < 50 copies/mL within the last 6 months.
are no follow-up data beyond 3 years for this regimen. Another option in patients who are virologically suppressed
Furthermore, virological suppression was lower in patients (VL < 50 copies/mL) whilst receiving a regimen of NNRTI +
+
with a CD4 count ≤ 200 cells/μL. Therefore, we do not two NRTIs, and who have never experienced virological
routinely recommend this regimen unless neither TDF nor failure, is a switch to the two-drug combination of DTG +
ABC can be used. Importantly, hepatitis B must be excluded RPV. Data from two clinical trials (SWORD I and II) showed
68
before considering this regimen as patients with hepatitis B that this regimen maintains virological suppression as a
must receive TDF + 3TC (or FTC) to prevent rapid emergence switch strategy in patients who have not previously
of 3TC resistance. The regimen should also not be used in experienced virological failure. This should not be done in
patients receiving RIF. patients who have chronic hepatitis B as TDF and 3TC (or
FTC) should always form a part of their treatment.
12. Management of patients
currently receiving first-line The recommended protocol for switching from a first-line
therapy NNRTI-based regimen to a DTG-based regimen is shown in
Figure 3.
Key points
Antiretroviral therapy options in patients failing first-line
ÿ Clinicians can consider switching patients who are non-nucleoside reverse transcriptase inhibitor-based
virologically suppressed on NNRTI-based first-line therapy
therapy from an NNRTI to DTG, whilst maintaining the In patients who are not virologically suppressed on an
same two-drug NRTI backbone. NNRTI-based regimen (VL > 50 copies/mL), we do not
ÿ In patients who are not virologically suppressed on an suggest an immediate switch to DTG with the same two
NNRTI-based regimen (VL > 50 copies/mL), we do not NRTIs. The reason for this is that it is possible that they have
recommend an immediate switch to DTG, but rather an developed resistance to the two NRTIs and may then be
enhanced adherence counselling with repeat VL placed on DTG without a fully effective drug to accompany
measurement in 2–3 months. If the VL remains it. In this scenario, we recommend for enhanced adherence
> 50 copies/mL, then these patients should be switched counselling and repeating the VL measurement in 2–3
to a second-line DTG regimen, which includes switching months. If the VL is < 50 copies/mL, then the patient can
the NRTI backbone. be switched to DTG + the same two NRTIs. If the VL is > 50

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