The role of dolutegravir in the management of HIV infection

Figures & data

Figure 1 Chemical structure of Tivicay^® (dolutegravir 50 mg tablets).

Table 1 Clinically relevant drug interactions

Medication	Effect with DTG	Action
Antiretrovirals
Efavirenz	Decreased DTG concentration	Increase DTG to 50 mg BID
Etravirine	Decreased DTG concentration	Avoid concomitant use unless atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir included in regimen
Fosamprenavir	Decreased DTG concentration	Increase DTG to 50 mg BID
Nevirapine	Decreased DTG concentration	Avoid combination
Tipranavir	Decreased DTG concentration	Increase DTG to 50 mg BID
Antiseizure medications
Carbamazepine	Decreased DTG concentration	Avoid combination
Phenytoin	Decreased DTG concentration	Avoid combination
Oxcarbazepine	Decreased DTG concentration	Avoid combination
Phenobarbital	Decreased DTG concentration	Avoid combination
Polyvalent cations
Aluminum hydroxide	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after aluminum hydroxide
Calcium salts	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after antacid or take DTG and calcium together with food
Iron salts	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after iron or take DTG and iron together with food
Magnesium salts	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after magnesium
Multivitamins and minerals	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after multivitamin or take DTG and multivitamin together with food
Sucralfate	Decreased DTG concentration	Administer DTG 2 hours before or 6 hours after sucralfate
Miscellaneous
Dofetilide	Increased dofetilide concentration	Avoid combination
Metformin	Increased metformin concentration	Monitor
Rifampin	Decreased DTG concentration	Increase DTG to 50 mg BID
St Johns Wort	Decreased DTG concentration	Avoid combination

Abbreviations: DTG, dolutegravir; BID, twice daily.

Table 2 Summary of dolutegravir (DTG) efficacy studies

Study	Primary outcomea	Safetyb
Treatment-naïve
SPRING-2^Citation39,Citation47	Noninferiority to raltegravir to reaching viral load <50 copies/mL at 48 and 96 weeks	Similar among raltegravir and DTG
SINGLE^Citation40,Citation48	Superiority to tenofovir/emtricitabine/efavirenz to reaching viral load <50 copies/mL at 48 and 96 weeks	Adverse effects more common in those on tenofovir/emtricitabine/efavirenz (43% vs 66%)
FLAMINGO^Citation41	Superiority to darunavir/ritonavir based regimens to reaching viral load <50 copies/mL at 48 weeks	Lipid measurements and study discontinuations higher in darunavir/ritonavir group
Treatment-experienced
SAILING^Citation42	Superior to raltegravir to reaching viral load <50 copies/mL at 48 weeks	Similar among raltegravir and DTG
VIKING^Citation43	Achievement of viral load <400 copies/mL by day 11 on dolutegravir monotherapy in 78% on once daily DTG and 96% on twice daily DTG	No serious adverse effects or no study discontinuations related to DTG
VIKING 3^Citation44	Achievement of viral load <50 copies/mL at 24 weeks in 69% when DTG added to failing regimen	Five study discontinuations related to DTG; three with hepatitis, one with cholelithiasis, and one with rash, pruritis, and paresthesia. One report of syncope and one hypersensitivity-type reaction.
IMPAACT P1093^Citation53,Citation54	Cohort one (ages 6–<12 years): achievement of viral load <400 copies/mL in 81.8% and <50 copies/mL in 63.6% Cohort two (ages 12–<18 years): achievement of viral load <400 copies/mL in 73.9% and <50 copies/mL in 60.9%	No serious adverse effects or study discontinuations related to DTG

Notes:

a Unless otherwise stated, DTG administered with optimized background regimen

b each trial demonstrated increased serum creatinine in patients taking dolutegravir.

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