Drug Database: GSK3640254

What is GSK3640254?

GSK3640254 is an investigational drug that is being studied to treat HIV infection.⁴

GSK3640254 belongs to a group of HIV drugs called maturation inhibitors.⁴ Maturation inhibitors work during the last stage of the HIV life cycle and interfere with the formation of mature, infectious virus. Specifically, maturation inhibitors block a long HIV protein chain called Gag from being broken up into smaller parts that are needed to create mature virus.⁵ This prevents HIV from multiplying, and can reduce the amount of HIV in the body.

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

Select clinical trials of GSK3640254

Study Name: NCT03784079

Phase: 2a
Status: This study has been completed.
Locations: Multiple countries, including United States
Purpose: The purpose of this study was to evaluate the antiviral activity, safety, and pharmacokinetics of GSK3640254 monotherapy given at various doses in adults who have never taken HIV medicines.^6,7
Selected Study Results: Results published in Clinical Infectious Diseases (2022) showed that GSK3640254 exhibited a dose-response relationship with antiviral activity. Doses of 40 mg or higher resulted in maximum average reductions in viral load levels of at least 1.0 log₁₀ copies/mL. The greatest antiviral effect was seen with the 140 and 200 mg doses, which produced viral load reductions of 1.5 and 2.0 log₁₀ copies/mL, respectively.⁷

Study Names: DOMINO; NCT04493216

Phase: 2b
Status: This study is ongoing, but not recruiting participants.
Locations: Multiple countries, including United States
Purpose: The purpose of this study is to evaluate the safety and efficacy of GSK3640254 (given at three different doses) compared to dolutegravir (brand name: Tivicay), each given in combination with abacavir/lamivudine (brand name: Epzicom) or emtricitabine/tenofovir alafenamide (brand name: Descovy), in adults who have never taken HIV medicines.³

Study Names: DYNAMIC; NCT04900038

Phase: 2b
Status: This study is ongoing, but not recruiting participants.
Locations:  Multiple countries, including United States
Purpose: The purpose of this study is to evaluate the safety, efficacy, and resistance profile of GSK3640254 (given at three different doses) in combination with dolutegravir, as compared to lamivudine (brand name: Epivir) in combination with dolutegravir, in adults who have never taken HIV medicines.⁸

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might GSK3640254 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the NCT03784079 study discussed under the previous section, 22 of 30 participants who received GSK3640254 experienced a side effect. Except for two side effects that were not related to GSK3640254, all side effects were mild to moderate in intensity. Overall, the most common side effects were headache and pain at the back of the throat. Gastrointestinal side effects were also noted to occur frequently. Side effects related to GSK3640254 treatment occurred in nine participants, with the most common being diarrhea, abdominal pain, and vomiting. There were no reports of drug-related serious side effects or treatment discontinuations because of side effects.⁹

Because GSK3640254 is still being studied, information on possible side effects of the drug is not complete. As testing of GSK3640254 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying GSK3640254?

More information about GSK3640254-related research studies is available from ClinicalTrials.gov. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

References

1. GSK Pipeline Report. Pipeline Changes. Accessed July 6, 2023
2. Jefferys R. Antiretroviral Therapy Pipeline 2022. Treatment Action Group Pipeline Report 2022. Accessed July 6, 2023
3. ViiV Healthcare. A Phase IIb, randomized, partially blind, active controlled, dose-range finding study of GSK3640254 compared to a reference arm of dolutegravir, each in combination with nucleoside reverse transcriptase inhibitors, in HIV-1 infected antiretroviral treatment-naive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 10, 2020. NLM Identifier: NCT04493216. https://clinicaltrials.gov/ct2/show/NCT04493216. Accessed July 6, 2023
4. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Accessed July 6, 2023
5. Pene Dumitrescu, Joshi SR, Xu J, et al. A Phase I evaluation of the pharmacokinetics and tolerability of the HIV-1 maturation inhibitor GSK3640254 and tenofovir alafenamide/emtricitabine in healthy participants. Antimicrob Agents Chemother. Published online March 22, 2021:AAC.02173-20, aac;AAC.02173-20v1. doi:10.1128/AAC.02173-20. Accessed July 6, 2023
6. ViiV Healthcare. A randomized, double-blind (sponsor-unblinded), placebo-controlled, adaptive trial to investigate the antiviral effect, safety, tolerability and pharmacokinetics of GSK3640254 in HIV-1 infected treatment-naïve adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 19, 2018. NLM Identifier: NCT03784079. Accessed July 6, 2023
7. Spinner CD, Felizarta F, Rizzardini G, et al. Phase IIa proof-of-concept evaluation of the antiviral efficacy, safety, tolerability, and pharmacokinetics of the next-generation maturation inhibitor GSK3640254. Clin Infect Dis. doi:10.1093/cid/ciab1065. Accessed July 6, 2023
8. ViiV Healthcare. A Phase IIb, randomized, double-blind, parallel-group study to assess the efficacy, safety, tolerability, and resistance profile of GSK3640254 in combination with dolutegravir compared to dolutegravir plus lamivudine in HIV-1 infected, treatment-naïve adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 19, 2021. NLM Identifier: NCT04900038. Accessed July 6, 2023
9. Spinner C, Felizarta F, Rizzardini G, et al. Phase IIA proof-of-concept trial of next-generation maturation inhibitor GSK3640254. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-10, 2021; Virtual. Accessed July 6, 2023