Dual Therapy With Dolutegravir + 3TC

Researchers in Argentina conducted a somewhat different experiment from the dolutegravir monotherapy clinical trials reported on earlier in this issue of TreatmentUpdate. They decided to use a simplified regimen of dolutegravir + 3TC (lamivudine) as the initial therapy for HIV infection. Compared to dolutegravir, 3TC is relatively weak. However, 3TC is generally well tolerated, would increase the antiviral effect of dolutegravir and is in widespread use in many countries as part of combination therapy for HIV.

For the study in Argentina (called Paddle), researchers recruited 20 participants who underwent frequent visits to the study's laboratory so that their blood could be drawn for analysis. Researchers wanted an initially intensive level of monitoring, as they were concerned about the possibility that a dual regimen may not be sufficiently powerful to significantly reduce and suppress viral load. In this report, we have the first 24-week results of Paddle; further results should be released later this year, as researchers continue the study for a total of 48 weeks. Researchers found that the combination of dolutegravir + 3TC was well tolerated and sufficiently effective in lowering viral loads.

Study Details

The average profile of participants at the start of the study was as follows:

• age -- 34 years

• 19 men, one woman

• viral load -- 24,000 copies/mL (about 4.4 logs)

• CD4+ count -- 500 cells/mm³

Results

During the first two weeks of the study, viral load fell rapidly by about 2 logs. After this time it declined more slowly. By the second week of the study, 11 participants had their viral loads fall below the 50-copy/mL mark. However, by the fourth week of the study, 85% of participants (17 out of 20) had their viral loads fall below the 50-copy/mL mark. The remaining three participants had viral loads of 288, 67 and 64 copies/mL respectively. By the eighth week of the study, all participants had an undetectable viral load.

Participants' CD4+ counts increased rapidly, reaching about 700 cells/mm³ at week 12 and stabilizing after that point.

Side Effects

Nearly all reported side effects were of mild intensity, such as the following:

• feeling sleepy during the daytime -- one person

• intestinal pain -- one person

• headache -- two people

• diarrhea -- one person

• nausea -- two people

The exception was a person who had a headache of moderate intensity.

These side effects occurred during the first week of the study and resolved shortly after.

Lab tests did not find any severely abnormal results.

For the Future

Researchers plan to continue this pilot study to the 48 week. Although the results are promising, much more research needs to be conducted.

Reference

Figueroa MI, Sued O, Patterson P, et al. Dolutegravir + lamivudine as initial treatment in HIV-infected, antiretroviral naïve patients: first results of the Paddle trial. 15 European AIDS Conference, 21-24 October 2015, Barcelona, Spain. Abstract LBPS Abstract PS4/1.