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Page 16 of 39 Guideline

BOX 1: Worked example of resistance testing. TABLE 11: Preferred initial antiretroviral therapy regimen for previously
A patient was prescribed 3TC + TDF + EFV. When the patient failed this regimen untreated patients.
after 1 year, the regimen was switched to 3TC + AZT + LPV/r. After 2 years, the First drug Second drug Third drug
patient failed this regimen too; therefore, resistance testing was performed. The
results showed the following: TDF 300 mg daily 3TC 300 mg daily, or FTC DTG 50 mg daily
200 mg daily
3TC/FTC: Resistant
3TC, lamivudine; DTG, dolutegravir; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.
TDF: Susceptible
ABC: Low-level resistance
AZT: Resistant Reasons for this preferred regimen are:
EFV: Resistant • This combination is available as a once-daily, one-tablet
LPV/r: Low-level resistance FDC from several suppliers.
Interpretation: • Tenofovir disoproxil fumarate is preferred over ABC
• Since the patient was receiving 3TC + AZT + LPV/r at the time of resistance
testing, it is possible to interpret the results reliably for these drugs. All three because of the risk of hypersensitivity reactions with ABC
drugs show at least a low level of resistance; thus, the patient should be
switched promptly to an alternative regimen. (HLA-B*5701 testing is not widely available in South
• Efavirenz shows resistance despite the patient not receiving the drug at the time Africa), certain studies showing lower VL suppression
of testing. This phenomenon is not uncommon with the K103N mutation.
• Tenofovir disoproxil fumarate shows susceptibility. The patient was previously with ABC when baseline VL is > 100 000 copies/mL
exposed to TDF, however. Although it is possible that none of the patient’s HIV 6
strains have evolved TDF resistance, the patient was not receiving the drug at (although not confirmed in a meta-analysis) and cost.
the time of resistance testing. Consequently, the possibility of archived • Lamivudine and FTC are regarded as interchangeable in
resistance to TDF cannot be excluded.
3TC, lamivudine; TDF, tenofovir disoproxil fumarate; EFV, efavirenz; AZT, zidovudine; LPV/r, terms of efficacy and safety.
lopinavir/ritonavir; ABC, abacavir; HIV, human immunodeficiency virus. • Dolutegravir is preferred over RAL and RPV because of its
higher resistance barrier. Raltegravir also requires a twice-
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• Conversely, it is only possible to identify mutations daily dosing and is not co-formulated in FDC. Dolutegravir
reliably for drugs that the patient was currently taking is preferred over EFV and PIs because superior efficacy and
when the resistance testing was performed, and for drugs tolerability were demonstrated in clinical trials. 12,13
affected by cross-resistance. ‘Susceptible’ results to drugs • There is an increasing prevalence of pre-treatment
for which there is no drug pressure may be unreliable resistance to NNRTIs in South Africa (> 10% in some
because of archived resistance. studies), which may compromise the efficacy of EFV-
° Common pitfall: Performing a resistance test in the based regimens. 64
absence of drug pressure. If the patient has defaulted
therapy for more than a few weeks, there is little Dolutegravir has been associated with a small but significant
purpose for a resistance test. In this scenario, it is risk of NTDs in women taking the drug during conception (0.3%
highly likely that the replication of wild-type virus vs. 0.1% in women on EFV at conception in a large Botswana
18
will overtake and obscure any resistant strain, birth outcomes surveillance study). This risk is lower than
rendering them undetectable by commercial resistance what was originally reported (see section 19). Women of
testing. childbearing potential should be counselled about the risks and
benefits of DTG and allowed to make an informed decision
11. Initial antiretroviral therapy regarding the use of DTG and contraception, in line with WHO
regimens for the previously 2019 recommendations. Dolutegravir has also been associated
with a greater weight gain than EFV. These issues have been
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untreated patient discussed in section 3.
Key points
Alternative initial antiretroviral therapy

ÿ In ART-naive patients, the preferred initial regimen is regimens
TDF (300 mg) + 3TC (300 mg) (or FTC 200 mg) + DTG Alternative regimens for previously untreated patients are
(50 mg) daily – available as a once-daily, one-tablet FDC. summarised in Table 12.
ÿ In patients receiving RIF, DTG dosing needs to be increased
to 50 mg twice-daily until 2 weeks after stopping RIF. Alternative initial antiretroviral therapy regimens in
ÿ Dolutegravir has been associated with a small excess risk specific clinical situations
of NTDs in women taking the drug during conception – There are specific clinical situations in which the preferred
WOCP should be counselled accordingly. combination of TDF + 3TC (or FTC) + DTG cannot be used
and the alternatives listed in Table 13 are advised instead.
Preferred initial antiretroviral therapy regimen
If both TDF and ABC are contraindicated and Hb is > 8 g/dL,
The preferred initial regimen for previously untreated then AZT can be considered as an alternative NRTI.
patients is summarised in Table 11.
Considerations for two-drug first-line regimen of
In patients receiving RIF, the DTG dose needs to be increased dolutegravir + lamivudine
to 50 mg twice daily until 2 weeks after stopping RIF. Other This regimen was shown to have an efficacy not inferior to a
drug–drug interactions with DTG are discussed in section 3 three-drug regimen in RCTs. However, these trials did not
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and section 17. include patients with a VL > 500 000 copies/mL, and there

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