Understanding ART regimens and formulations

Clinical description

• ART requires combining 3 different ARVs that act differently to avoid development of drug-

resistant HIV.

• Use only the standard ARV regimens for the specified patient groups shown in these guidelines.

Other ARV combinations may cause more side effects or lead to drug-resistant HIV. Non- standard (NS) regimens can only be prescribed by specialists for complicated cases.

• Do not change ART regimens without a clear medical indication. Unnecessary regimen changes

spoil future treatment options.

• 1st Line regimens are the best. Patients can remain on the same 1st line regimen possibly for

life if they are fully adherent. All 1st line regimens:

o Are easy to prescribe and easy to take.

o Have a low risk of serious side effects. Do not require lab monitoring for toxicity.

o There are 8 different regimens used as 1st line

• Two are standard for initiating ART depending on patient age and weight (see

Table 16 on page 68).

o Transition patients with significant side effects to an alternative regimen without delay.

Choose the regimen by substituting only the ARV responsible for the side effects.

• 2nd Line regimens are for patients with confirmed treatment failure on 1st line regimen. Moving

from 1st to 2nd line ART is called switching. 2nd line regimens:

o Contain protease inhibitors (PI) or integrase strand transfer inhibitors (INSTI).

o PI- and INSTI-based regimens may be used as 1st or 2nd line. It is therefore no longer possible to distinguish 1st and 2nd line regimens without knowing the patient’s regimen history.

o There are 8 different regimens that may be used as 2nd line. The appropriate 2nd line regimen is determined by the 1st line regimen that the patient was taking when failing.

Patients suspected to fail on a PI- or INSTI-based regimen need genotyping to confirm the presence of drug resistant virus before switching to 2nd or 3rd line.

• 3rd Line regimens are for patients with confirmed treatment failure on 2nd line regimen. This

requires confirmation of drug resistant virus using genetic testing in the lab. 3rd line can only be initiated by a specialised ARV clinician upon authorization of the national HIV Drug Resistance Committee. 3rd line regimens are:

o Expensive o Can have more side effects and are more difficult to take.

• It is no longer recommended to give a 7-day NRTI “tail” when stopping ART in patients on EFV-

based regimens. The risk of developing EFV resistance due to the longer half-life is now considered insignificant.

Understanding ART regimens and formulations

• DTG may be used in 1st, 2nd and 3rd line ART regimens.
• The benefits of DTG outweigh any potential risks, including for women who may get pregnant

while on ART:

o Faster and more durable viral suppression o Lower risk of maternal OIs and death o Reduced risk of HIV transmission to sexual partners and to the child o The potential risk of neural tube defects is now considered very low.

• Note: regimen 13A can only be used from 30kg+ as TDF-dose is too high for smaller children.
• (Relative) Contra-indications for DTG-based regimens:

o Renal failure: creatinine clearance <30ml/min o Sev. liver damage: ascites; albumin <2.8g/dL; tot. bilirubin >50mmol/L; encephalopathy

• Potential side-effects (rare). Submit ADR reporting form for all suspected side-effects

o Insomnia, headache, agitation o Nausea, diarrhoea o Skin rash o Weight gain, hyperglycaemia o Hepatitis/jaundice (uncommon)

• DTG can cause obesity in some patients, requiring a regimen substitution.

o Unwanted weight gain can undermine motivation for ART adherence o Obesity can cause diabetes, hypertension and the long-term consequences o This potential side effect has not yet been seen in children.

• DTG can potentially cause or worsen hyperglycaemia

o Monitor blood glucose every 12 months in patients 40 years+ o In patients with newly diagnosed or worsened hyperglycaemia on DTG-based regimen:

substitute DTG for EFV or other alternative regimen and check if glucose improves

• Important DTG drug-interactions:

o Rifampicin (TB treatment): double daily DTG-dose (see section 17 on page 82).

o Drugs with iron, magnesium, calcium, zinc (FeFo, multi-vitamins, antacids, etc.) reduce DTG absorption: take DTG 2 hours before or 6 hours after taking such drugs.

o Metformin (diabetes): limit daily dose to 1000mg, confirm effective glucose control.

o NVP, ETR (ARVs): do not combine with DTG o Carbamazepine, phenytoin, phenobarbitone, sodium valproate: avoid DTG.