Drug information

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Other Names:
744 LA, CAB, CAB LA, GSK-1265744, GSK1265744, GSK744, GSK744 LA, GSK744 LAP, S-265744, S/GSK1265744, cabotegravir LA, cabotegravir long-acting injectable, cabotegravir sodium
Drug Class:
Integrase Inhibitors
Molecular Formula:

C19 H17 F2 N3 O5

Registry Number:
1051375-10-0 (CAS)
Chemical Name:

(3S,11aR)-N-((2,4-difluorophenyl)methyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo(3,2-a)pyrido(1,2-d)pyrazine-8-carboxamide

Chemical Class:
Carbamoyl pyridone
Organization:
ViiV Healthcare
Phase of Development:

Cabotegravir is in Phase 3 development for both HIV treatment and HIV prevention. Patients who do not qualify for or are unable to participate in the Phase 3 clinical studies of cabotegravir for HIV treatment may be able to obtain the drug through an expanded access (also called compassionate use) treatment program. For details on the program, go to ClinicalTrials.gov (NCT03462810).

An application for marketing approval of a long-acting two-drug regimen consisting of cabotegravir and rilpivirine for HIV treatment was submitted to the U.S. Food and Drug Administration (FDA) in April 2019. The submission to FDA also included an application for approval of an oral formulation of cabotegravir.

Chemical Image: (Click to enlarge)

cabotegravir

Molecular Weight: 405.3553

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 HIV/AIDS (Auckland, N.Z.) article,3 HIV Treatment Bulletin article,4 ClinicalTrials.gov,5 and ViiV Healthcare press release6)

Pharmacology

Pharmacology

Mechanism of Action: HIV-1 integrase strand transfer inhibitor (INSTI). Cabotegravir (CAB), an analog of dolutegravir, prevents viral DNA integration into the host genome and inhibits HIV replication. CAB is being developed for both HIV treatment and HIV prevention.3,4,7

CAB oral tablets and a long-acting injectable two-drug regimen consisting of CAB and rilpivirine (RPV) for the treatment of HIV infection has been approved by Health Canada and is currently under regulatory review by the U.S. FDA and the European Medicines Agency (EMA).6,8,9

Half-life (T½): In a study of CAB LA (long-acting parenteral [LAP] nanosuspension) administered via intramuscular (IM) or subcutaneous (SC) injection, the mean apparent terminal phase half-life ranged from 21 to 50 days. Following oral dosing, the CAB half-life was 40 hours.10

The pharmacokinetic tail phase associated with CAB LA was assessed in both the ECLAIR (NCT02076178) and HPTN 077 (NCT02178800) HIV prevention trials. In the ECLAIR study where CAB LA 800 mg was administered IM every 12 weeks to men without HIV, the apparent terminal plasma half-life of CAB was 18 days after the first injection and 40 days after the third injection. In 17 percent of participants, plasma CAB was detectable at 52 weeks post injection. In the HPTN 077 study, male and female participants received CAB LA 800 mg IM every 12 weeks or 600 mg IM every 8 weeks. The apparent terminal half-life of CAB was 42.5 days in males and 64.6 days in females. The median time for plasma CAB to drop below detectable levels was 42.7 weeks in males and 66.3 weeks in females. At 76 weeks post final injection, 58% of females and 87% of males had plasma CAB concentrations below detectable levels.11-14

Metabolism/Elimination: CAB is primarily metabolized by UGT1A1 (main pathway) and UGT1A9 (minor pathway). CYP-mediated metabolism is expected to have a minimal role in CAB metabolism.15 Following a single oral radiolabeled dose of CAB 30 mg, 58.5% of the administered dose was recovered in feces (primarily as unchanged drug) and 26.8% was recovered in urine (as a glucuronide metabolite [M1]).16

Resistance: Data through Week 48 of the Phase 3 ATLAS trial (NCT02951052) demonstrated that VF was infrequent across both study arms. Three participants in the CAB LA plus RPV LA (long-acting rilpivirine injection) group, all with HIV-1 subtype A/A1 or AG, had confirmed VF. At the time of failure, one participant had the E138A reverse-transcriptase (RT) resistance-associated mutation (RAM) and one participant had both the E138K plus V108I RT RAMs. Both of these participants, however, had pre-existing NNRTI mutations at baseline. The E138E/K RT mutation and the N155H INSTI mutation were identified in a third participant at the time of failure.Two of the participants with VF and HIV-1 subtype A/A1 also had the L74I integrase mutation at baseline. The L74I integrase mutation itself, however, does not descrease susceptibility to CAB.17,18

In the Phase 3 FLAIR trial (NCT02938520), Week 48 results also demonstrated a low rate of VF in both study arms. Four participants in the CAB LA plus RPV LA group had confirmed VF. Three of the four participants had treatment-emergent NNRTI and INSTI resistance with the following RAMs: E138E/A/K/T plus Q148R in one participant, K101E plus G140R in another participant, and E138K plus Q148R in a third participant. All three participants were noted to have HIV-1 subtype A1 and the L74I INSTI mutation at baseline. One other participant, who had HIV-1 subtype AG, had VF during oral dosing and withdrew from the study prior to receiving LA therapy. In this participant, no resistance mutations were detected.19,20

In the Phase 3b ATLAS-2M trial (NCT03299049), participants were randomized to CAB LA plus RPV LA administered every 8 weeks (Q8W) or CAB LA plus RPV LA administered every 4 weeks (Q4W). Results at Week 48 found that confirmed VF occurred in eight participants in the Q8W group and in two participants in the Q4W group. Five of the eight confirmed VFs in the Q8W group were found to have baseline pre-existing RAMs to RPV alone or both RPV and CAB. Treatment-emergent RAMs to RPV (K101E, E138K, M230L), CAB (N155H, Q148R, E138K), or both RPV and CAB were identified in five out of eight confirmed VFs in the Q8W group and in both of the confirmed VFs in the Q4W group.21,22

Select Clinical Trials

Select Clinical Trials


Cabotegravir for HIV Treatment

Study Identifiers: ATLAS; NCT02951052
Sponsor: ViiV Healthcare
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label study is to evaluate the safety and efficacy of switching adults with HIV from a current suppressive ART regimen to CAB LA plus RPV LA.
Study Population:

  • Participants are adults with HIV who have been on a stable ART regimen consisting of two NRTIs plus an INSTI, NNRTI, or PI for at least 6 months prior to screening.
  • Participants have HIV RNA <50 copies/mL in the 12 months prior to and at screening.
  • Participants must not have any primary resistance to INSTIs or NNRTIs (with the exception of K103N).23

Selected Study Results:


Study Identifiers: FLAIR; NCT02938520
Sponsor: ViiV Healthcare
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label trial is to evaluate the safety and efficacy of CAB LA plus RPV LA for the maintenance of virologic suppression following a switch from abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in treatment-naive adults.
Study Population:

  • Participants are treatment-naive adults with HIV who have HIV RNA ≥1000 copies/mL.
  • Participants must not have any primary resistance to NNRTIs (with the exception of K103N) and have no known INSTI resistance.24

Selected Study Results:

Study Identifiers: LATITUDE; ACTG A5359; NCT03635788
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label study is to compare the safety, efficacy, and durability of CAB LA plus RPV LA versus oral standard of care (SOC) ART in adults with a history of suboptimal adherence and control of their HIV infection.
Study Population:

  • Participants are adults with HIV who have evidence of nonadherence to ART.
  • Participants have HIV RNA >200 copies/mL within 60 days of study entry.
  • Investigators, along with participants, are able to form an oral ART regimen for induction therapy that includes at least three antiretrovirals, two of which are fully active.
  • Participants must not have resistance-associated mutations to RPV or INSTIs.25


Study Identifiers: ATLAS-2M; NCT03299049
Sponsor: ViiV Healthcare
Phase: 3b
Status: This study is ongoing, but not recruiting participants.
Study Purpose: The purpose of this open-label trial is to evaluate the safety and efficacy of CAB LA plus RPV LA administered every 8 weeks (Q8W) or every 4 weeks (Q4W) in adults with HIV who are virologically suppressed.
Study Population:

  • Participants are adults with HIV who have either been 1) continuously receiving an oral SOC ART regimen for at least 6 months prior to screening or 2) receiving CAB LA plus RPV LA Q4W or “current ART” in the ATLAS study through at least study Week 52.
  • All participants have HIV RNA <50 copies/mL at screening. Participants receiving oral SOC who have not participated in ATLAS must also have had HIV RNA <50 copies/mL in the past 12 months prior to screening.21

Selected Study Results:


Additional studies evaluating CAB LA for HIV treatment are currently ongoing or are planned, including:

  • MOCHA (NCT03497676): A Phase 1/2 study evaluating the safety, acceptability, tolerability, and pharmacokinetics of oral CAB and CAB LA plus RPV LA in virologically suppressed children and adolescents with HIV. This study is ongoing, but not recruiting participants.26
  • ACTG A5357 (NCT03739996): A Phase 2 study evaluating whether CAB LA plus the broadly neutralizing antibody (bNAb) VRC07-523LS can maintain viral suppression in adults with HIV. This study is currently recruiting participants.27
  • NCT04001803 and NCT04399551: Two Phase 3 studies evaluating implementation strategies for CAB LA plus RPV LA in the United States and in European countries, respectively. NCT04001803 is ongoing, but not recruiting. See the ClinicalTrials.gov record for the status of NCT04399551.28,29


Cabotegravir for HIV Prevention

Study Identifiers: ECLAIR; NCT02076178
Sponsor: ViiV Healthcare
Phase: 2a
Status: This study has been completed.
Study Purpose: The ECLAIR study evaluated the safety, tolerability, and acceptability of CAB LA for pre-exposure prophylaxis (PrEP).
Study Population:

  • Participants were men without HIV who were not at high risk of acquiring HIV.11,30

Selected Study Results:


Study Identifiers: HPTN 077; NCT02178800
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 2a
Status: This study has been completed.
Study Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAB LA.
Study Population:

  • Participants were men and women without HIV who are at low risk of acquiring HIV.13,31

Selected Study Results:


Study Identifiers: HPTN 083; NCT02720094
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 2b/3
Status: See the ClinicalTrials.gov record for this study's status.
Study Purpose: The purpose of this study is to compare the safety and efficacy of CAB LA to oral tenofovir DF/emtricitabine (Truvada) for PrEP.
Study Population:

  • Participants do not have HIV and are in general good health.
  • Participants are cisgender men and transgender women who have sex with men and are at high risk of acquiring HIV.32

Selected Study Results:


Study Identifiers: HPTN 084; NCT03164564
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Phase: 3
Status: This study is currently recruiting participants.
Study Purpose: The purpose of this study is to compare the safety and efficacy of CAB LA to oral Truvada for PrEP.
Study Population:

  • Participants are women who are sexually active and do not have HIV but who are at risk of acquiring HIV.33

Adverse Events

Adverse Events


ATLAS (NCT02951052)

In the Phase 3 ATLAS trial, 308 participants were randomized in each treatment arm to either continue on their current oral ART regimen or switch to CAB LA plus RPV LA (after a lead-in with oral CAB plus RPV). Week 48 results found that 86% of participants in the LA group versus 71% of participants in the oral ART group experienced an adverse event (AE) (excluding injection site reactions [ISRs]). Drug-related AEs (excluding ISRs) occurred in 29% of participants in the LA group and 3% of participants in the oral ART group. Besides ISRs, the most common drug-related AEs with LA therapy were fatigue, pyrexia, headache, and nausea, each occurring in 4% of LA participants. The majority of the drug-related AEs that occurred in the LA group were mild or moderate. Only 3% of participants in the LA group withdrew from the study because of a non-ISR AE. There were no reports of drug-related serious adverse events (SAEs) in the LA group.17

ISRs were commonly reported throughout the study, but the majority of ISRs were Grade 1 or 2 in intensity and resolved within seven days. Four participants withdrew from the study because of ISRs. The most common ISR among participants receiving CAB LA plus RPV LA was injection-site pain, occurring in 75% of participants.17,34


FLAIR (NCT02938520)

The Phase 3 FLAIR trial randomized 283 participants per treatment arm to either continue with oral ART (DTG/ABC/3TC) or switch to CAB LA plus RPV LA (after a lead-in with oral CAB plus RPV). Data from Week 48 showed that AEs (excluding ISRs) were reported in 87% of participants in the LA group and 80% of participants in the oral ART group. Excluding ISRs, drug-related AEs occurred in 28% of participants receiving CAB LA plus RPV LA versus 10% of participants receiving oral ART. With LA therapy, headache and pyrexia were the most common drug-related AEs (excluding ISRs), and each occurred in 5% of participants in the LA group. Most of the drug-related AEs that occurred in the LA arm were mild or moderate in intensity. Only 3% of participants in the LA arm withdrew from the study because of a non-ISR AE. One drug-related SAE was reported in the LA arm—right knee monoarthritis.19

In the FLAIR trial, ISRs were common; injection-site pain was the most frequently reported ISR, and led to the withdrawal of two participants. Two additional participants withdrew from the study because of injection intolerability. The incidence of ISRs decreased over time, and most ISRs were Grade 1 or 2 and lasted for a median of three days.19,35


ATLAS-2M (NCT03299049)
Week 48 results from the ATLAS-2M trial found a similar safety profile between the CAB LA plus RPV LA Q8W dosing group (n = 522) and the CAB LA plus RPV LA Q4W dosing group (n = 523). Drug-related AEs occurred in 21% of participants in the Q8W group and 24% of participants in the Q4W group. The majority of drug-related AEs (96%) were Grade 1-2 in severity. Five participants (<1%) in the Q8W group and eight participants (2%) in the Q4W group experienced a drug-related AE that led to study withdrawal. Drug-related SAEs (presyncope and acute pancreatitis) occurred in two participants in the Q8W arm, while one participant in the Q4W arm experienced a drug-related SAE (allergic reaction).21,36

Most of the ISRs that occurred during the study were Grade 1-2 and lasted for a median of three days. Injection-site pain was the most commonly reported ISR. Study discontinuations because of injection-related reasons occurred in six participants (1%) in the Q8W group and 11 participants (2%) in the Q4W group.36


ECLAIR (NCT02076178)
In the 41-week ECLAIR study, 106 participants were randomly assigned to CAB and 21 participants were randomly assigned to placebo. Nineteen participants withdrew from the CAB group: one before treatment, 11 during or after oral therapy but prior to injections, and seven during the injection period. Of the seven CAB participants who withdrew during the injection phase, four withdrew because of injection intolerability.37

Overall, AEs occurred at a similar rate in both the CAB and placebo groups (CAB 96%; placebo 90%). However, Grade 2 or higher AEs occurred more frequently with CAB (80% of participants) than with placebo (48% of participants), mainly because of injection site pain. During the oral dosing phase, treatment-related AEs, most of which were Grade 1 to 2, occurred in 36% of CAB participants versus 14% of placebo participants. No SAEs occurred during oral dosing. During the injection period, 93% of CAB participants versus 57% of placebo participants reported an ISR. The majority of CAB participants had ISRs that were Grade 1 (80%) or 2 (56%), while 19% of CAB participants experienced Grade 3 ISRs. Ninety-two percent of the ISRs that occurred in the CAB group were cases of injection-site pain, lasting an average duration of 5.4 days. Other ISRs occurring in the CAB group included mild pruritus, nodules/bumps, warmth to touch, bruising, and induration.37


HPTN 077 (NCT02178800)

The HPTN 077 study enrolled 110 participants into Cohort 1 (800 mg every 12 weeks) and 90 participants into Cohort 2 (600 mg every 8 weeks), with a total of 151 participants who received CAB and 48 who received placebo. Ten participants discontinued CAB because of drug-related AEs: two during oral therapy and eight during the injection phase. Reasons for CAB discontinuation included one gastrointestinal event, three rash/urticaria events, and six neurologic events. Four SAEs were reported among CAB participants: vertigo, transient weakness, laryngitis (unrelated), and acute kidney injury (unrelated).31

During the injection phase, Grade 2 or higher AEs occurred in 91% of participants in the CAB group versus 88% of participants in the placebo group. The most common Grade 2 or higher AE was decreased creatinine clearance, occurring with similar frequency in each arm. ISRs were the only Grade 2 or higher AEs that were significantly more common with CAB than placebo. Among participants receiving CAB, ISRs (mostly Grade 1 to 2) occurred in 92% of participants in Cohort 1 and 88% of participants in Cohort 2. There was only one participant who discontinued CAB due to an ISR. Two CAB participants (one in each cohort) had a Grade 3 ISR, although neither event resulted in product discontinuation.31


HPTN 083 (NCT02720094)
In the HPTN 083 trial, 4,566 participants were eligible to receive either CAB LA plus placebo or oral Truvada plus placebo. Analysis of final results from the blinded phase of the study found that injection site reactions occurred in 80.9% of participants receiving CAB LA versus 31.2% of participants receiving placebo injections. The majority of injection site reactions with CAB LA were Grade 1 or 2 in intensity. Only 2.2% of CAB LA participants discontinued treatment because of an injection-related AE. Increased blood glucose levels, pyrexia, and nasopharyngitis were more common in the CAB LA group than in the Truvada group.32,38

Drug Interactions

Drug Interactions

CAB is primarily metabolized by UGT1A1, with minor contributions from UGT1A9. Physiologically based pharmacokinetic (PBPK) modeling suggests that potent UGT1A1 or UGT1A9 inhibitors (such as atazanavir or mefenamic acid) will not have a clinically relevant impact on CAB exposures. Weak to moderate UGT inducers (such as phenobarbital) also appear to be safe for coadministration with CAB; however, potent UGT inducers are predicted to significantly decrease concentrations of CAB.39

Oral CAB does not affect the pharmacokinetics of midazolam in human study participants, indicating that CAB is neither a CYP inhibitor nor inducer. In vitro, CAB does not inhibit UGT enzymes, except UGT1A3. CAB, however, is predicted to have no clinically significant effect on UGT1A3 substrates. CAB does not inhibit hepatic, intestinal, or renal drug transporters (Pgp, BCRP, BSEP, MRP2, OCT1, OATP1B1, OAT1B3, MATE1, MATE2-K, MRP4, OCT2), except for OAT1 and OAT3 (OAT1/3).15,40PBPK modeling predicts a minimal risk of drug-drug interactions when OAT1/3 substrates (such as tenofovir, cidofovir, and methotrexate) are coadministered with CAB.41

Coadministration of oral CAB with an oral contraceptive containing levonorgestrel (LNG) and ethinyl estradiol (EE) did not affect the pharmacokinetics of LNG or EE, suggesting CAB can be administered in combination with LNG- and EE-containing oral contraceptives without clinically significant interactions.42In the HPTN 077 trial (NCT02178800) involving women without HIV, CAB LA concentrations during injections and during the pharmacokinetic tail was unaffected by concomitant hormonal contraceptive use (regardless of contraception type).11,43

There are no apparent pharmacokinetic interactions between oral CAB and etravirine or between oral CAB and RPV.44,45

Coadministration of steady-state rifampin (RIF) 600 mg with a single-dose of oral CAB 30 mg increased CAB oral clearance by 2.4-fold and decreased CAB AUC(0-∞) by 59% compared to CAB administered alone. The coadministration of RIF with oral CAB 30 mg once daily is not recommended. The impact of RIF on the long-acting IM formulations of CAB and RPV was evaluated in an in silico study. Results indicated that coadministration of RIF 600 mg with CAB LA and RPV LA would likely lead to suboptimal concentrations of both CAB and RPV.46,47

In a drug-drug interaction study of rifabutin (RBT) 300 mg on the pharmacokinetics of oral CAB 30 mg in healthy male participants, RBT was shown to have a modest effect on plasma CAB concentrations. Plasma CAB trough concentrations, however, remained above the necessary level to maintain viral suppression in individuals with HIV.48

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: cabotegravir. https://chem.nlm.nih.gov/chemidplus/rn/1051375-10-0. Accessed July 13, 2020
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed July 13, 2020
  3. Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. HIVAIDS Auckl NZ. 2016;8:157-164.
  4. Collins S and Clayden P, eds. HIV pipeline 2019: new drugs in development. HIV Treatment Bulletin. 2019 Jul; 20(1) Suppl: 1-10. HIV Treatment Bulletin. http://i-base.info/htb/wp-content/uploads/2019/07/PIPELINE-2019-FINAL-full-version.pdf. Accessed July 13, 2020
  5. ViiV Healthcare. GSK1265744 (Cabotegravir, CAB) for named patient/compassionate use in HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 5, 2018. NLM Identifier: NCT03462810. https://www.clinicaltrials.gov/ct2/show/NCT03462810. Accessed July 13, 2020
  6. ViiV Healthcare: Press Release, dated April 29, 2019. ViiV Healthcare submits New Drug Application to US FDA for the first monthly, injectable, two-drug regimen of cabotegravir and rilpivirine for treatment of HIV. https://www.viivhealthcare.com/en-gb/media/press-releases/2019/april/viiv-healthcare-submits-new-drug-application-to-us-fda-for-the-first-monthly-injectable-two-drug-regimen-of-cabotegravir-and-rilpivirine-for-treatment-of-hiv/. Accessed July 13, 2020
  7. Karmon SL, Markowitz M. Next-generation integrase inhibitors: where to after raltegravir? Drugs. 2013;73(3):213-228.
  8. ViiV Healthcare ULC. Vocabria and Cabenuva: product monograph, March 2020. Health Canada. https://pdf.hres.ca/dpd_pm/00055411.PDF. Accessed July 13, 2020
  9. ViiV Healthcare: press release, dated July 29, 2019. ViiV Healthcare submits regulatory application to European Medicines Agency for investigational cabotegravir to be used in combination with rilpivirine as the first monthly, injectable treatment for HIV. https://viivhealthcare.com/en-gb/media/press-releases/2019/july/viiv-healthcare-submits-regulatory-application-to-european-medic/. Accessed July 13, 2020
  10. Spreen W, Ford S, Chen S, et al. Pharmacokinetics, safety and tolerability of the HIV integrase inhibitor S/GSK1265744 long acting parenteral nanosuspension following single dose administration to healthy adults. Abstract presented at: International AIDS Conference; July 22-27, 2012; Washington DC. Abstract TUPE040. http://www.abstract-archive.org/Abstract/Share/11509. Accessed July 13, 2020
  11. ViiV Healthcare. A Phase IIa study to evaluate the safety, tolerability and acceptability of long acting injections of the HIV integrase inhibitor, GSK1265744, in HIV uninfected men (ECLAIR). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2014. NLM Identifier: NCT02076178. https://clinicaltrials.gov/ct2/show/NCT02076178. Accessed July 13, 2020
  12. Ford S, Stancil B, Markowitz M, more authors. ECLAIR study of cabotegravir LA injections: characterization of safety and PK during the “PK tail” phase. Abstract presented at: HIV Research for Prevention (HIVR4P); October 17-21, 2016; Chicago, IL. Abstract OA12.06LB. https://www.liebertpub.com/doi/pdf/10.1089/aid.2016.5000.abstracts. Accessed July 13, 2020
  13. National Institute of Allergy and Infectious Diseases (NIAID). A Phase IIa study to evaluate the safety, tolerability and pharmacokinetics of the investigational injectable HIV integrase inhibitor, GSK1265744, in HIV-uninfected men and women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2014. NLM Identifier: NCT02178800. https://clinicaltrials.gov/ct2/show/NCT02178800. Accessed July 13, 2020
  14. Landovitz R. Tail-phase safety, tolerability and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected individuals: HPTN 077 final results. Webcast presented at: HIV Research for Prevention (HIVR4P); October 21-25, 2018; Madrid, Spain. http://webcasts.hivr4p.org/console/player/40424?mediaType = slideVideo&&crd_fl = 1&ssmsrq = 1560986504079&ctms = 5000&csmsrq = 983. Accessed July 13, 2020
  15. Reese M, Ford S, Bowers G, et al. In vitro drug interaction profile of the HIV integrase inhibitor, GSK1265744, and demonstrated lack of clinical interaction with midazolam. Abstract presented at: 15th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy; May 19-21, 2014; Washington, DC. Abstract P_20. http://regist2.virology-education.com/abstractbook/2014_4.pdf. Accessed July 13, 2020
  16. Culp A, Bowers G, Gould E, et al. Metabolism, excretion, and mass balance of the HIV integrase inhibitor, cabotegravir (GSK1265744) in humans. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. http://www.natap.org/2014/ICAAC/ICAAC_41.htm. Accessed July 13, 2020
  17. Swindells S. Long-acting cabotegravir rilpivirine as maintenance therapy: ATLAS Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41308?mediaType = slideVideo&&crd_fl = 0&ssmsrq = 1552603335674&ctms = 5000&csmsrq = 5060. Accessed July 13, 2020
  18. Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112-1123. doi:10.1056/NEJMoa1904398
  19. Orkin C. Long-acting cabotegravir rilpivirine for HIV maintenance: FLAIR Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41309?mediaType = slideVideo&&crd_fl = 0&ssmsrq = 1552868268167&ctms = 5000&csmsrq = 5056. Accessed July 13, 2020
  20. Orkin C, Arasteh K, Górgolas Hernández-Mora M, et al. Long-acting cabotegravir and rilpivirine after oral induction for HIV-1 infection. N Engl J Med. 2020;382(12):1124-1135. doi:10.1056/NEJMoa1909512
  21. ViiV Healthcare. A Phase IIIb, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of long-acting cabotegravir plus long-acting rilpivirine administered every 8 weeks or every 4 weeks in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 2, 2017. NLM Identifier: NCT03299049. https://clinicaltrials.gov/ct2/show/NCT03299049. Accessed July 13, 2020
  22. Overton ET, Richmond GJ, Rizzardini G, et al. Cabotegravir rilpivirine every 2 months is noninferior to monthly: ATLAS-2M study. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Boston, MA. Abstract 34. https://www.croiconference.org/abstract/cabotegravir-rilpivirine-every-2-months-is-noninferior-to-monthly-atlas-2m-study/. Accessed July 13, 2020
  23. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of switching to long-acting cabotegravir plus long-acting rilpivirine from current INI- NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02951052. https://clinicaltrials.gov/ct2/show/NCT02951052. Accessed July 13, 2020
  24. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, open-label study evaluating the efficacy, safety, and tolerability of long-acting intramuscular cabotegravir and rilpivirine for maintenance of virologic suppression following switch from an integrase inhibitor single tablet regimen in HIV-1 infected antiretroviral therapy naive adult participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02938520. https://clinicaltrials.gov/ct2/show/NCT02938520. Accessed July 13, 2020
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Last Reviewed: July 13, 2020