Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV

What to Start

Integrase Strand Transfer Inhibitor–Based Regimens as Initial Antiretroviral Therapy

Four oral integrase strand transfer inhibitors (INSTIs)—bictegravir (BIC), dolutegravir (DTG), elvitegravir (EVG), and raltegravir (RAL)—are approved for use in people with HIV as their initial ARV treatment. Intramuscular cabotegravir (CAB) is approved for use with rilpivirine (RPV) (with or without an oral CAB + RPV lead-in) as part of a long-acting injectable complete antiretroviral (ARV) regimen to replace a stable oral regimen in people with HIV and viral suppression. The role of this combination is discussed in the Optimizing Antiretroviral Therapy in the Setting of Viral Suppression section. Long-acting injectable cabotegravir (CAB-LA) is also approved for pre-exposure prophylaxis (PrEP). The first-generation INSTIs EVG and RAL have some disadvantages, which include a low barrier to resistance. In addition, because EVG has to be given with cobicistat (COBI), a pharmacokinetic (PK) booster, it has a high potential for drug–drug interactions, whereas RAL-based regimens have a higher pill burden than other INSTI regimens. Because of these disadvantages, elvitegravir/cobicistat (EVG/c) and RAL are no longer recommended by the Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) as initial ART. Because the second-generation INSTIs BIC and DTG have high barriers to resistance, BIC/tenofovir alafenamide (TAF)/‌emtricitabine (FTC) and DTG plus TAF/FTC or tenofovir disoproxil fumarate (TDF)/FTC are recommended for most people with HIV (see Appendix B, Table 6 for more information on the INSTIs BIC and DTG).

This section of the guidelines will focus on BIC and DTG, the two INSTIs recommended by the Panel as part of the Recommended Initial Regimens for Most People With HIV (Table 6a) and Other Initial Antiretroviral Regimens for Certain Clinical Scenarios (Table 6b) (see Tables 6a and 6b and Table 7).

Panel’s Recommendations for Integrase Strand Transfer Inhibitor–Based Regimens as Initial Therapy

The Panel recommends one of the following INSTI-based regimens as initial ART for people with HIV who do not have a history of using CAB-LA as PrEP (see Table 6a in Initial Combination Antiretroviral Regimens for People With HIV):

• BIC/TAF/FTC (AI)
• DTG plus (TAF or TDF) with (FTC or lamivudine [3TC]) (AI)
• DTG/3TC (AI), except for those with HIV RNA >500,000 copies/mL, with hepatitis B virus (HBV) coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.

INSTI resistance has been reported in people who acquired HIV following exposure to CAB-LA as PrEP.¹ For a person who has had exposure to CAB-LA as PrEP, an INSTI-containing regimen should not be initiated unless an INSTI genotypic resistance test result is available and shows no INSTI-resistance mutations (AIII). If treatment is initiated before genotypic test results are available, boosted darunavir (DRV) plus (TAF or TDF) plus (FTC or 3TC) should be used, pending INSTI resistance results (AIII). See Table 6a in Initial Combination Antiretroviral Regimens for People With HIV for more details.

Because of the low rates of transmitted INSTI resistance in the United States at present, when there is suspicion that HIV was acquired from a partner with virologic failure while on an INSTI, an INSTI‑based regimen can be started pending the results of the INSTI genotype test.

For people who have never used CAB-LA for PrEP and who acquired HIV despite using INSTI-based post-exposure prophylaxis, an INSTI genotype should be obtained prior to beginning an INSTI-based regimen. However, because selection of INSTI-resistant virus is likely to be uncommon in this setting, an INSTI-based regimen could be started prior to the return of genotype results (CIII).

The Panel also recommends using DTG/abacavir (ABC)/3TC (BI) when concerns about renal or bone-associated adverse events preclude the use of TAF or TDF. However, ABC should only be given to people who are documented to be HLA-B*5701-negative.

Adverse Effects

BIC and DTG are generally well tolerated, although there are reports of insomnia in some people. Depression and suicidal ideation, primarily in people with a history of psychiatric illnesses, have been reported rarely in those receiving INSTI-based regimens.^2-5

Among people with HIV who have not yet received ART, initiation of INSTI-containing regimens has been associated with greater weight increases compared to non-nucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI) regimens.^6-11 In randomized trials of ARV-naive individuals, the mean increase in weight from baseline associated with BIC and DTG was similar and greater than with EVG/c or with efavirenz (EFV).^8,12-14 Weight gain was also greater in those initiating TAF than other nucleoside reverse transcriptase inhibitors (NRTIs).^7,8,15 These weight increases appear to disproportionately affect women and Black and Hispanic people,^6-8,16 yet predictors and mechanisms for the weight gain are still unclear. In general, concerns for weight gain should not be a reason to avoid an INSTI- or TAF-based regimen.

Integrase Strand Transfer Inhibitor Use in People of Childbearing Potential

Clinicians should refer to the Perinatal Guidelines for detailed recommendations on ARV regimens in treatment-naive people, including recommendations on the use of INSTI-based regimens during conception and throughout pregnancy.

• Earlier data from a birth outcomes surveillance study in Botswana raised concern about an increased risk of neural tube defects (NTDs) (0.9%) in infants born to women who were receiving DTG at the time of conception.^17,18 Updated data from the same study showed that the prevalence of NTDs in infants born to women on DTG at the time of conception is not significantly different from those on non-DTG regimens at the time of conception.¹⁹ Based on these data, DTG is now the preferred INSTI for pregnant individuals with HIV. See the Perinatal Guidelines for further discussion.
• BIC is recommended as an alternative INSTI during pregnancy because data about safety, PK, and efficacy in pregnancy are available but are more limited than data about drugs classified as Preferred by the Perinatal Guidelines. See the Perinatal Guidelines for more details.

Bictegravir

BIC is approved by the U.S. Food and Drug Administration for initial therapy in adults with HIV as a component of a once-daily single-tablet regimen with TAF and FTC.

Efficacy in Clinical Trials

• The efficacy of BIC in ART-naive adults has been evaluated in two large Phase 3 randomized double-blind clinical trials that compared BIC to DTG administered in combination with two NRTIs. The primary efficacy endpoint was the proportion of participants with plasma HIV RNA <50 copies/mL at Week 48.
  • The GS-US-380-1490 trial randomized participants 1:1 to receive either BIC/TAF/FTC or DTG with coformulated TAF/FTC. Both regimens were given once daily. At Week 96, 84% of participants in the BIC arm and 86% of those in the DTG arm achieved HIV RNA <50 copies/mL.¹⁵
  • The GS-US-380-1489 trial randomized participants 1:1 to receive BIC/TAF/FTC or coformulated DTG/ABC/3TC once daily. At Week 96, 88% of participants in the BIC/TAF/FTC arm and 90% of those in the DTG/ABC/3TC arm achieved HIV RNA <50 copies/mL.²⁰
  • Week 144 follow-up from both trials demonstrated noninferiority of the BIC/TAF/FTC regimen to both DTG-containing regimens, with high levels of virologic suppression and no treatment-emergent resistance.

Adverse Effects

• BIC is generally well tolerated.
• Neuropsychiatric adverse events have been reported with INSTIs. BIC-associated serious neuropsychiatric effects were uncommon (<1%) in clinical trials and mainly occurred in the setting of preexisting depression, other psychiatric illness, or prior suicide attempt.²¹

Drug–Drug Interactions

Note: See Table 24d for a comprehensive list of potential INSTI-related drug–drug interactions.

• BIC is a cytochrome P450 (CYP) 3A4 substrate and a uridine diphosphate glucuronosyltransferase (UGT) 1A1 substrate; therefore, its metabolism may be affected by concomitant use of CYP3A4 and UGT1A1 inducers or inhibitors. Rifampin or other rifamycins may decrease BIC or TAF concentrations, which may result in loss of therapeutic effect of the ART. For people who require rifamycins, BIC/FTC/TAF should not be used. Use of certain anti‑seizure medications and St. John’s wort should also be avoided.²¹
• BIC is an inhibitor of the drug transporters OCT2 (organic cation transporter 2) and MATE1 (multidrug and toxic compound extrusion 1); therefore, BIC may increase concentrations of drugs that are substrates of these transporters. For this reason, dofetilide is contraindicated with BIC/TAF/FTC.
• Like other INSTIs, oral absorption of BIC may be reduced when BIC is coadministered with polyvalent cations (e.g., aluminum-, magnesium-, or calcium-containing antacids; calcium or iron supplements).

Other Factors and Considerations

• BIC decreases tubular secretion of creatinine without affecting glomerular function. Increases in serum creatinine are observed typically within the first 4 weeks of BIC therapy (with a median increase of 0.10 mg/dL after 48 weeks). This increase is comparable to that seen with other ARV drugs that have a similar effect on creatinine secretion, including DTG, RPV, and COBI.
• Treatment-emergent mutations that confer BIC resistance have rarely been reported in people receiving BIC for initial therapy.²² BIC has not been studied in prospective trials for people with prior INSTI failure or INSTI-related resistance mutations. One analysis of 20 individuals with preexisting INSTI-related resistance mutations showed maintenance of virologic suppression in 19 people after switch to BIC, and viral suppression after beginning BIC in one person without prior ARV treatment. There are, however, insufficient data at present to recommend BIC use in such cases.

The Panel’s Recommendation

The Panel recommends the use of BIC/TAF/FTC as a Recommended Initial Regimen for Most People With HIV (AI) (see Table 6a and Table 7 for more detailed recommendations).

Dolutegravir

As initial ARV regimens, both DTG plus two NRTIs and DTG/3TC demonstrated high efficacy in achieving HIV suppression in clinical trials. DTG is given once daily, with or without food.

Efficacy in Clinical Trials

The efficacy of DTG in ART-naive individuals has been evaluated in several fully powered randomized controlled clinical trials. In these trials, DTG-based regimens were noninferior or superior to a comparator INSTI-, NNRTI-, or PI-based regimen. The primary efficacy endpoint in these clinical trials was the proportion of participants with plasma HIV RNA <50 copies/mL.^13,23,24

DTG Plus Two NRTIs Versus Other INSTIs Plus Two NRTIs

• DTG-based regimens (with TAF/FTC or ABC/3TC) have been compared to BIC/TAF/FTC in two randomized controlled trials. These regimens have virologic efficacy that is similar to BIC/TAF/FTC (see discussion in the BIC section above).^15,20,23,25

DTG Plus Two NRTIs Versus EFV Plus Two NRTIs

• The SINGLE trial compared DTG 50 mg once daily plus ABC/3TC to EFV/TDF/FTC in 833 participants. At Week 48, DTG plus ABC/3TC was superior to EFV/TDF/FTC, primarily because the study treatment discontinuation rate was higher in the EFV arm than in the DTG arm.²⁶ At Week 144, DTG plus ABC/3TC remained superior to EFV/TDF/FTC.²⁷
• The ADVANCE trial, an open-label, noninferiority trial conducted in South Africa, compared DTG with either TDF/FTC or TAF/FTC to EFV/TDF/FTC. At Week 96, the DTG-based regimens were noninferior to the EFV regimen based on the proportion of participants with HIV RNA levels <50 copies/mL (79% in DTG/TAF/FTC vs. 78% in DTG/TDF/FTC vs. 74% in EFV/TDF/FTC arms). More participants discontinued the trial regimen in the EFV group than in the DTG group. Mean weight gain was 7.1 kg in the DTG/TAF/FTC group, 4.3 kg in the DTG/TDF/FTC group, and 2.3 kg in the EFV/TDF/FTC group and was greater among women than men.¹⁴

DTG Plus Two NRTIs Versus Ritonavir-Boosted Darunavir Plus Two NRTIs

• The FLAMINGO study, a randomized open-label clinical trial, compared DTG 50 mg once daily to the boosted PI—darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily—each administered in combination with investigator-selected ABC/3TC or TDF/FTC. At Week 48, DTG was superior to DRV/r, with 90% and 83% of participants achieving HIV RNA <50 copies/mL, respectively. More participants discontinued their assigned regimen in the DRV/r arm.²⁸ The difference in efficacy between the DTG and DRV/r regimens was more pronounced in people with pre-treatment HIV RNA levels >100,000 copies/mL. At Week 96, DTG remained superior to DRV/r.²⁹

DTG/3TC

• In the GEMINI-1 and GEMINI-2 trials, 1,433 ART-naive participants with baseline HIV RNA <500,000 copies/mL and no evidence of HBV infection were randomized to receive DTG plus 3TC or DTG plus TDF/FTC. At Week 96, DTG plus 3TC was noninferior to DTG plus TDF/FTC with 86% of participants in the DTG plus 3TC group and 89.5% in the DTG plus TDF/FTC group with viral load <50 copies/mL.³⁰ Virologic nonresponse was uncommon, occurring in 3.1% of participants who received DTG plus 3TC and 2% of participants who received DTG plus TDF/FTC. No treatment-emergent NRTI or INSTI resistance occurred in either treatment group. Among participants who started the study with CD4 counts <200 cells/mm³, the rate of HIV RNA <50 copies/mL at Week 96 was lower in the DTG plus 3TC group than in the DTG plus TDF/FTC group; however, the difference was not related to a higher rate of virologic failure in the two-drug group. Overall mean change in weight from baseline was 3.1 kg in the DTG plus 3TC group and 2.1 kg in the DTG plus TDF/FTC group. At Week 144, DTG plus 3TC maintained noninferiority to DTG plus TDF/FTC with 82% versus 84% of participants maintaining viral load <50 copies/mL, respectively. The proportion of participants with viral load ≥50 copies/mL was 3% in both treatment groups. A lower risk of drug-related adverse events was found with DTG plus 3TC versus DTG plus TDF/FTC (20% vs. 27%; relative risk, 0.76 [95% confidence interval, 0.63–0.92]).³⁰
• Two other small, nonrandomized single-arm studies showed similar rates of viral suppression with DTG plus 3TC.^31,32

Adverse Effects

• DTG is generally well tolerated. The most reported adverse reactions of moderate-to-severe intensity were insomnia and headache.
• Some studies have shown greater weight increase among people initiating INSTI-based regimens, including regimens with DTG.^7,8,33,34 In a pooled analysis of eight randomized controlled trials in ART-naive individuals, the weight gain at 96 weeks with BIC- and DTG-‍based regimens was similar (approximately 3.5 kg). The clinical significance of weight gain in this setting is unclear.⁸
• Neuropsychiatric adverse events (e.g., sleep disturbances, depression, anxiety, suicidal ideation) associated with the initiation of DTG and other INSTIs have been reported.^2,3,35,36 However, analyses of data from large randomized controlled trials and a health care database demonstrated similar rates of neuropsychiatric adverse events between DTG-based regimens and regimens that included RAL, EFV, DRV, and ATV.³⁷ Neuropsychiatric events rarely led to DTG discontinuation.

Drug–Drug Interactions

Note: See Table 24d for a comprehensive list of potential INSTI-related drug–drug interactions.

• DTG has fewer drug interactions than BIC.
• DTG oral absorption may be reduced when the ARV is coadministered with polyvalent cations. DTG should be taken at least 2 hours before or 6 hours after cation-containing antacids or laxatives are taken. Alternatively, DTG and supplements containing calcium or iron can be taken simultaneously with food.

Other Factors and Considerations

• DTG decreases tubular secretion of creatinine without affecting glomerular function, with increases in serum creatinine observed within the first 4 weeks of treatment.
• Treatment-emergent mutations that confer DTG resistance have been rarely reported in people receiving DTG as part of a three-drug regimen for initial therapy.^38-40 The incidence of resistance with DTG is much lower than with EVG or RAL, which suggests that DTG, like BIC, has a higher barrier to resistance than EVG or RAL.

The Panel’s Recommendations

• The Panel classifies the following as Recommended Initial Regimens for Most People With HIV (see Table 6a and Table 7 for more detailed recommendations):
  • DTG plus (TAF or TDF) plus (FTC or 3TC) (AI)
  • DTG/3TC (AI)—not recommended for those with HIV RNA >500,000 copies/mL, with HBV coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.
• The Panel recommends DTG/ABC/3TC (BI) in certain clinical scenarios for people with HIV who are documented to be HLA-B*5701-negative and who have concerns about renal or bone toxicities associated with TAF or TDF. This regimen should not be used in people with HBV coinfection unless an HBV-active drug (i.e., entecavir) other than 3TC is used.

References

1. Marzinke MA, Fogel JM, Wang Z, et al. Extended analysis of HIV infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. Antimicrob Agents Chemother. 2023;67(4):e0005323. Available at: https://pubmed.ncbi.nlm.nih.gov/36995219.
2. Kheloufi F, Allemand J, Mokhtari S, Default A. Psychiatric disorders after starting dolutegravir: report of four cases. 2015;29(13):1723-1725. Available at: https://pubmed.ncbi.nlm.nih.gov/26372287.
3. Harris M, Larsen G, Montaner JS. Exacerbation of depression associated with starting raltegravir: a report of four cases. 2008;22(14):1890-1892. Available at: https://pubmed.ncbi.nlm.nih.gov/18753871.
4. Penafiel J, de Lazzari E, Padilla M, et al. Tolerability of integrase inhibitors in a real-life setting. J Antimicrob Chemother. 2017;72(6):1752-1759. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28333231.
5. Hoffmann C, Welz T, Sabranski M, et al. Higher rates of neuropsychiatric adverse events leading to dolutegravir discontinuation in women and older patients. HIV Med. 2017;18(1):56-63. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27860104.
6. Bernardino JI, Mocroft A, Wallet C, et al. Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: a substudy of the NEAT001/ANRS143 randomised trial. PLoS One. 2019;14(1):e0209911. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30689664.
7. Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med. 2019;381(9):803-815. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31339677.
8. Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clin Infect Dis. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31606734.
9. Bourgi K, Jenkins CA, Rebeiro PF, et al. Weight gain among treatment-naive persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada. J Int AIDS Soc. 2020;23(4):e25484. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32294337.
10. Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2020;70(7):1267-1274. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31100116.
11. Bedimo R, Li X, Adams-Huet B, et al. Differential BMI changes following PI- and INSTI-based ART initiation by sex and race. Presented at: Conference on Retroviruses and Opportunistic Infections. 2019. Seattle, WA. https://www.natap.org/2019/CROI/croi_81.htm.
12. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020;7(6):e389-e400. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32504574.
13. Calmy A, Tovar Sanchez T, Kouanfack C, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV. 2020;7(10):e677-e687. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33010241.
14. Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV. 2020;7(10):e666-e676. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33010240.
15. Stellbrink HJ, Arribas JR, Stephens JL, et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e364-e372. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31068272.
16. Bedimo R, Adams-Huet B, Taylor BS, Lake J, Luque A. Integrase inhibitor-based HAART is associated with greater BMI gains in blacks, hispanics and women. Presented at: IDWeek. 2018. San Fransisco, CA. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254938
17. Zash R, Holmes L, Makhema J, et al. Surveillance for neural tube defects following antiretroviral exposure from conception. Presented at the 22nd International AIDS Conference (AIDS 2018). 2018. Amsterdam, the Netherlands. https://www.natap.org/2018/IAC/IAC_52.htm.
18. Zash R, Makhema J, Shapiro RL. Neural-tube defects with dolutegravir treatment from the time of conception. N Engl J Med. 2018;379(10):979-981. Available at: https://pubmed.ncbi.nlm.nih.gov/30037297.
19. Zash R, Holmes L, Diseko M, et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo study, Botswana. Presented at the 11th IAS Conference on HIV Science. 2021. Virtual. Available at: https://www.natap.org/2020/IAC/IAC_112.htm.
20. Wohl DA, Yazdanpanah Y, Baumgarten A, et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019;6(6):e355-e363. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31068270.
21. Gilead. BIKTARVY [package insert]. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210251s010lbl.pdf.
22. Chamberlain N, Mena L, Brock JB. Case report: emergent resistance in a treatment-naive person with human immunodeficiency virus under bictegravir-based therapy. Open Forum Infect Dis. 2021;8(6):ofab297. Available at: https://pubmed.ncbi.nlm.nih.gov/34189182.
23. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. 2017;390(10107):2063-2072. Available at: https://pubmed.ncbi.nlm.nih.gov/28867497.
24. Orrell C, Hagins DP, Belonosova E, et al. Fixed-dose combination dolutegravir, abacavir, and lamivudine versus ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate and emtricitabine in previously untreated women with HIV-1 infection (ARIA): week 48 results from a randomised, open-label, non-inferiority, phase 3b study. Lancet HIV. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28729158.
25. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. 2017;390(10107):2073-2082. Available at: https://pubmed.ncbi.nlm.nih.gov/28867499.
26. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807-1818. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24195548.
27. Walmsley S, Baumgarten A, Berenguer J, et al. Brief report: dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial. J Acquir Immune Defic Syndr. 2015;70(5):515-519. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26262777.
28. Clotet B, Feinberg J, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. 2014. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24698485.
29. Molina JM, Clotet B, van Lunzen J, et al. Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naive HIV-1-positive individuals: 96 week results from FLAMINGO. J Int AIDS Soc. 2014;17(4 Suppl 3):19490. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25393999.
30. Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naive adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31834000.
31. Cahn P, Rolon MJ, Figueroa MI, Gun A, Patterson P, Sued O. Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study. J Int AIDS Soc. 2017;20(1):1-7. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28537061.
32. Nyaku AN, Zheng L, Gulick RM, et al. Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353. J Antimicrob Chemother. 2019;74(5):1376-1380. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30668695.
33. Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis. 2019;70(7). Available at: https://www.ncbi.nlm.nih.gov/pubmed/31100116.
34. Bourgi K, Jenkins C, Rebeiro PF, et al. Greater weight gain among treatment-naive persons starting integrase inhibitors. Presented at: Conference on Retroviruses and Opportunistic Infections. 2019. Seattle, WA. Available at: https://www.croiconference.org/sessions/greater-weight-gain-among-treatment-naive-persons-starting-integrase-inhibitors.
35. Hoffmann C, Llibre JM. Neuropsychiatric adverse events with dolutegravir and other integrase strand transfer inhibitors. AIDS Rev. 2019;21(1):4-10. Available at: https://pubmed.ncbi.nlm.nih.gov/30899113.
36. Rubin LH, O’Halloran JA, Williams DW, et al. Integrase inhibitors are associated with neuropsychiatric symptoms in women with HIV. J Neuroimmune Pharmacol. 2023;18(1-2):1-8. Available at: https://pubmed.ncbi.nlm.nih.gov/35178611.
37. Fettiplace A, Stainsby C, Winston A, et al. Psychiatric symptoms in patients receiving dolutegravir. J Acquir Immune Defic Syndr. 2017;74(4):423-431. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27984559.
38. Fulcher JA, Du Y, Zhang TH, Sun R, Landovitz RJ. Emergence of integrase resistance mutations during initial therapy containing dolutegravir. Clin Infect Dis. 2018;67(5):791-794. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29933437.
39. Pena MJ, Chueca N, D’Avolio A, Zarzalejos JM, Garcia F. Virological failure in HIV to triple therapy with dolutegravir-based firstline treatment: rare but possible. Open Forum Infect Dis. 2019;6(1):ofy332. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30631792.
40. Lubke N, Jensen B, Huttig F, et al. Failure of dolutegravir first-line ART with selection of virus carrying R263K and G118R. N Engl J Med. 2019;381(9):887-889. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31461601.