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Page 6 of 39 Guideline

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ritonavir (LPV/r). Importantly, at least one fully active TABLE 3: Dosage and common adverse drug reactions of integrase strand
NRTI was genotypically confirmed at baseline in this trial. transfer inhibitors available in southern Africa.
Drug Recommended dosage Common or severe ADR
RAL 400 mg 12 hourly Headache and other CNS side effects,
Data from the Tsepamo surveillance study in Botswana gastrointestinal upset, hepatitis and rash
demonstrated a statistically higher rate of neural-tube (rare), rhabdomyolysis (rare). Weight
gain.
defects (NTDs) amongst women who were taking DTG at DTG 50 mg daily Insomnia, headache and other CNS side
the time of conception (0.3% vs. 0.1% in women receiving effects, gastrointestinal upset, hepatitis
and rash (rare). Possibly teratogenic.
other ARTs in the periconception period). Unlike in South Weight gain.
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Africa, folate fortification of staple foods does not occur in ADR, adverse drug reaction; CNS, central nervous system; DTG, dolutegravir; RAL, raltegravir.
Botswana. In contrast to the Botswana data, no NTDs were
reported in a Brazilian cohort of 1468 women, 382 of whom TABLE 4: Key drug–drug interactions with dolutegravir.
Action required
Drug
were DTG-exposed. Although additional data will RIF Administer DTG twice daily (i.e. 50 mg 12 hourly)
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undoubtedly be forthcoming, it should be noted that the until 2 weeks after stopping RIF.
absolute risk is < 0.5%, which may be outweighed by the Metformin Do not exceed metformin 500 mg 12 hourly.
additional benefits of DTG over alternative therapies. We Carbamazepine, phenytoin Give alternative anticonvulsant if possible (e.g.
lamotrigine or topiramate). If carbamazepine is
recommend that women of childbearing potential (WOCP), used, then administer DTG 12 hourly. Avoid
phenytoin with DTG altogether.
particularly those who wish to become pregnant or who Polyvalent cation-containing For magnesium-/aluminium-containing antacids,
have no reliable access to effective contraception, should be agents (e.g. antacids, laxatives, administer > 2 h after or > 6 h before DTG dose. For
iron/calcium supplements, either take with food or
sucralfate, iron and calcium
counselled adequately about the potential risks and benefits supplements) apply intervals above.
of DTG- versus EFV-based ART and should be offered a Etravirine Do not use DTG + etravirine together unless a
choice of first-line regimens. boosted PI is also used in the combination.
DTG, dolutegravir; RIF, rifampicin; PIs, protease inhibitors.
Common side effects encourage appropriate exercise and dietary measures to
Dolutegravir and RAL are generally well tolerated, with limit this.
most side effects being mild and very rarely leading to
discontinuation. Dolutegravir may cause a mild increase in Dosage and common adverse drug reactions (ADRs) of
serum creatinine because of interference with tubular InSTIs are described in Table 3.
secretion. This does not represent renal damage and is not an
indication of switching to another drug. The rise in creatinine Key drug–drug interactions with dolutegravir
occurs within the first few weeks and persists for as long as Key drug–drug interactions involving DTG are summarised
the patient remains on DTG.
in Table 4.
° Common pitfall: Assuming that the rise in creatinine
° Common pitfall: Forgetting to dose DTG twice daily
seen in patients on DTG necessarily represents when RIF-based tuberculosis treatment is commenced.
renal failure. In reality, the effect of DTG on creatinine
secretion is of no consequence and does not represent 4. Non-nucleoside reverse
a decline in renal function.
transcriptase inhibitor class of
Raltegravir and DTG can cause headaches when started, but antiretroviral drugs
this usually resolves. These drugs may also cause insomnia
and neuropsychiatric side effects. Raltegravir and DTG can Key points
occasionally cause hypersensitivity rashes, including life- ÿ Efavirenz remains a good first-line ART option for
threatening rashes. Weight gain is more pronounced in patients who tolerate DTG poorly, or where DTG is
patients taking an InSTI as part of their ART regimen (with contraindicated or declined.
the exception of cabotegravir, which is not currently available ÿ Efavirenz 400 mg is not inferior to EFV 600 mg and offers
in South Africa). Black women, patients with low baseline a somewhat improved side-effect profile. However, it is
+
CD4 counts and patients with high baseline VLs appear to currently not available in FDC and has not been well
be at greatest risk. The risk also appears to be moderated by studied in patients receiving rifampicin (RIF)-based TB
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the companion drugs in the patient’s ART regimen. In the treatment or in pregnant women.
ADVANCE trial, women on a tenofovir alafenamide (TAF) + ÿ Rilpivirine (RPV) is another good first-line option, but it
FTC + DTG regimen were found to gain a median of 10 kg is not available in FDC, cannot be co-administered with
over 96 weeks, with little evidence of a plateau in the RIF-based TB treatment and should not be started in
increase. In women, median weight gain in the same period patients with a VL > 100 000 copies/mL.
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in the TDF + FTC + DTG arm was 5 kg, and 3 kg in the TDF ÿ Nevirapine (NVP) is no longer recommended for new
+ FTC + EFV arm. In men, weight gain was approximately patients because of its adverse side effect profile.
half as much in each arm. The long-term health implications ÿ Etravirine (ETR) may be used as part of third-line therapy
of these findings are currently unclear; however, clinicians where appropriate, but is not recommended as a first-line
should be aware of the possibility of weight gain and agent.

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