ART Guidelines
References
Key points - In ART-naïve patients, the preferred initial regimen is TDF (300 mg) + 3TC (300 mg) (or FTC 200 mg) + DTG (50 mg) daily – available as a once-daily, one-tablet FDC.
- In patients receiving RIF, DTG dosing needs to be increased to 50 mg twice daily until 2 weeks after stopping RIF.
- DTG has been associated with a small excess risk of neural-tube defects (NTDs) in women taking the drug at conception – women of childbearing potential (WOCP) should be counselled accordingly.
Preferred initial antiretroviral therapy regimen
The preferred initial regimen for previously untreated patients is summarised in Table 11.
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| TABLE 11: Preferred initial antiretroviral therapy regimen for previously untreated patients. | ||
| First drug | Second drug | Third drug |
|---|---|---|
| TDF 300 mg daily | 3TC 300 mg daily; or FTC 200 mg daily | DTG 50 mg daily |
|
3TC, lamuvidine; DTG, dolutegravir; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate. |
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In patients receiving RIF, the DTG dose needs to be increased to 50 mg twice daily until 2 weeks after stopping RIF. Other drug-drug interactions with DTG are discussed in Module 3 and Module 17.
Reasons for this preferred regimen are:
- This combination is available as a once-daily, one-tablet FDC from several suppliers.
- TDF is preferred over ABC due to: the risk of hypersensitivity reactions with ABC (HLA-B*5701 testing is not widely available in SA); certain studies showing lower VL suppression with ABC when baseline VL > 100 000 copies/mL (although not confirmed in a meta-analysis);6 and cost.
- 3TC and FTC are regarded as interchangeable in terms of efficacy and safety.
- DTG is preferred over RAL and RPV because of its higher resistance barrier.63 RAL also requires twice-daily dosing and is not co-formulated in FDC. DTG is preferred over EFV and PIs because superior efficacy and tolerability were demonstrated in clinical trials.12,13
- There is an increasing prevalence of pre-treatment resistance to NNRTIs in South Africa (> 10% in some studies) which may compromise efficacy of EFV-based regimens.64
DTG has been associated with a small excess risk of neural-tube defects (NTDs) in women taking the drug at conception (0.3% vs. 0.1% in women on EFV at conception in a large Botswana birth-outcomes surveillance study).18 This risk is lower than originally reported (see Module 19). WOCP should be counselled about this risk and the benefits of DTG, and allowed to make an informed decision regarding the use of DTG and contraception, in line with World Health Organization (WHO) 2019 recommendations. DTG has also been associated with greater weight gain than EFV.21 These issues are discussed in Module 3.
Alternatives regimens for the previously untreated patient are summarised in Table 12.
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| TABLE 12: Alternative initial antiretroviral therapy regimens for the previously untreated patient. | |
| Regimen | Notes |
|---|---|
| TDF + 3TC (or FTC) + EFV |
|
| TDF + 3TC (or FTC) + RPV |
|
| ABC + 3TC + DTG |
|
|
3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; EFV, efavirenz; FDC, fixed-dose combination; FTC, emtricitabine; LTFU, loss to follow-up; RIF, rifampicin; RPV, rilpivirine; TDF, tenofovir disoproxil fumarate; VL, viral load. |
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Alternative initial antiretroviral therapy regimens in specific clinical situations
There are specific clinical situations in which the preferred combination of TDF + 3TC (or FTC) + DTG cannot be used and the alternatives listed in Table 13 are advised instead.
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| TABLE 13: Recommended alternative initial antiretroviral therapy regimens in specific clinical situations where TDF + 3TC (or FTC) + DTG cannot be used. | |
| Scenario | Alternative regimen |
|---|---|
| Renal impairment at baseline (CrCl < 50 mL/min) | ABC + 3TC + DTG† |
| Renal impairment develops on TDF | ABC + 3TC + DTG |
| Patient is intolerant of DTG side-effects | TDF + 3TC (or FTC) + EFV (or RPV) |
| Pure red cell aplasia develops due to 3TC/FTC | TDF + DTG (can then add AZT when Hb has recovered) (or RPV + DTG, provided that VL is suppressed) |
|
3TC, lamivudine; ABC, abacavir; AZT, zidovudine; CrCl, creatinine clearance rate; DTG, dolutegravir; EFV, efavirenz; FTC, emtricitabine; Hb, haemoglobin; RPV, rilpivirine; TDF, tenofovir disoproxil fumarate; VL, viral load. †, In such patients, if renal function subsequently improves (CrCl > 50 mL/min), then they can be switched to TDF + 3TC + DTG. |
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If both TDF and ABC are contraindicated and Hb > 8 g/dL, then AZT can be considered as an alternative NRTI.
This regimen was shown to have an efficacy not inferior to a three-drug regimen in RCTs.67 However, these trials did not include patients with a VL > 500 000 copies/mL and there are no follow-up data beyond 3 years for this regimen. Furthermore, virological suppression was lower in patients with a CD4+ count ≤ 200 cells/μL. Therefore, we do not routinely recommend this regimen unless neither TDF nor ABC can be used. Importantly, HBV must be excluded before considering this regimen as patients with HBV must receive TDF + 3TC (or FTC) to prevent rapid emergence of 3TC resistance. The regimen should also not be used in patients receiving RIF.