TreatmentUpdate
224

January 2018 

Preliminary results of dolutegravir + 3TC for initial therapy of HIV

Dolutegravir (Tivicay and in Triumeq) is a powerful integrase inhibitor that is used by many HIV-positive people as part of combination HIV therapy (ART). 3TC (lamivudine) is a nuke (nucleoside analogue) that has been used for two decades and is generally safe and well tolerated.

Researchers in the U.S. with the AIDS Clinical Trials Group (ACTG) conducted a pilot study to gain some preliminary understanding of the potential for dolutegravir-3TC as an initial therapy for HIV.

Researchers recruited 120 participants who had not previously been exposed to treatment and gave them the following combination:

  • dolutegravir 50 mg + 3TC 300 mg, both once daily

At the 24th week of the study, 90% of participants had a viral load less than 50 copies/mL. One person whose treatment failed developed HIV that was resistant to both dolutegravir and 3TC. The results from this study should be considered preliminary, as the study is expected to continue for a total of 52 weeks.

Large clinical trials are underway to compare the effectiveness and safety of dolutegravir-3TC vs. dolutegravir + TDF + FTC.

Study details

Researchers recruited adults who had not previously taken ART, whose viral load was less than 500,000 copies and who did not have HIV with resistance to major classes of treatment (nukes, non-nukes, protease inhibitors, integrase inhibitors). Also, none of the participants were co-infected with hepatitis B virus (HBV).

The average profile of participants upon study entry was as follows:

  • age – 30 years
  • 87% men, 13% women
  • CD4+ count – 387 cells/mm3
  • viral load – 41,000 copies/mL
    (High viral loads: Note that 19% of participants had a viral load between 100,000 and 200,000 copies/mL and 12% had a viral load greater than 200,000 copies/mL but less than 500,000 copies/mL)

Results

Overall, at week 24, 90% of participants had an undetectable viral load. When researchers sorted participants by their pre-study viral loads, the proportions with viral suppression at week 24 were as follows:

  • participants with an initial viral load greater than 100,000 copies/mL – 89% had a suppressed viral load at week 24
  • participants with an initial viral load of 100,000 copies/mL or less – 90% had a suppressed viral load at week 24

Seven participants left the study and/or stopped taking dolutegravir-3TC before week 24 for the following reasons:

  • moved – two people
  • imprisonment – one person
  • lost contact with clinic – one person
  • became pregnant – one person
  • unable to take study drugs exactly as directed – one person
  • unable to visit the study clinic – one person

At week 24, five participants had detectable viral loads. Here are more details about them:

  • Two participants had detectable viral loads prior to week 24, one of whom entered the study with a viral load greater than 100,000 copies/mL. At week 24 their viral loads were between 50 and 200 copies/mL; by the study’s design their viral loads were not high enough to be considered virological failure. The researchers referred to those two detectable viral loads as “non-success.”
  • Three other participants had virological failure prior to week 24, one of whom entered the study with a viral load greater than 100,000 copies/mL. One participant repeatedly missed taking doses of the study medicines and quit the study at week 18. This participant developed resistance to 3TC and some integrase inhibitors. Researchers found that blood samples from all three participants had very low levels of dolutegravir, suggesting that they were not taking the drug.

At week 24, CD4+ cell counts increased by about 167 cells/mm3.

Ninety percent of participants disclosed perfect adherence.

Safety

Two people developed serious adverse effects that were possibly related to the study medicines, as follows:

  • severe kidney dysfunction
  • sometimes, a racing heart beat when at rest

No neuropsychiatric side effects were reported.

None of the participants left the study because of side effects.

Bear in mind

The study results should be considered preliminary. Further results will be made available in the future, as the study is expected to continue for 52 weeks. Larger trials of dolutegravir-3TC are planned or underway.

—Sean R. Hosein

REFERENCE:

Taiwo BO, Marconi VC, Berzins B, et al. Dolutegravir plus lamivudine maintain HIV-1 suppression through week 48 in a pilot randomized trial. Clinical Infectious Diseases. 2018; in press.