October 26, 2015
The first results -- in small numbers of people for short periods of time -- showed that viral load generally stayed undetectable for the 24 weeks. However, viral load did not stay undetectable for everyone. Some people were unlucky. And when viral load did rebound, some of these people developed drug resistance.
Although the possibility of using fewer drugs might sound tempting, the risks are also real.
Two studies reported on two-drug (dual) therapy using dolutegravir with 3TC.
The first was an oral presentation from Argentina called the PADDLE study.2
This study involved 20 people (average age 34) who had never used HIV drugs and who started their first treatment using dolutegravir plus 3TC. Viral load was measured eight times over the first month and then weekly. This means that the study involved close monitoring and a lot of clinic visits. As an additional caution, the researchers only expanded the study to 20 people when the first 10 people had been shown good response over the first 8 weeks.
Also importantly, nearly everyone started with a low viral load and the average was 20,000 copies/mL. However, although this was not intended when planning the study, four people started with a viral load greater than 100,000 copies/mL. These high results were because of viral load increases between the screening visit and the start of the study.
After starting treatment, viral load dropped very quickly. Within three weeks, everyone saw their viral load fall to less than 400 copies/mL, with ten people getting undetectable <50 copies/mL within 2 weeks. By 8 weeks, all 20 participants had a viral load that was less than 50 copies/mL -- with the people starting at highest viral load taking longest to reach undetectable. Although many people might find this surprising, this aspect of the study was expected by the researchers. Other studies have reported how quickly integrase inhibitors reduce viral load within the first month of treatment.
What was more remarkable was that all 20 people stayed undetectable through to week 12 and then to week 24.
Average CD4 counts increased by about 200 cells/mm3 -- as would be expected with triple combinations. Very few side effects were reported and nearly all were mild. The most serious side effect was a moderate headache (but with minimal need for medication) and there were no serious abnormalities from blood monitoring tests (ie not needing an additional intervention). The PADDLE study will continue to follow participants for two years and larger studies are already planned.
The second dual therapy study was presented as a poster in the exhibition hall and had a different design and studied people with a different HIV history.3
In this case, 27 French patients who were already on treatment and who had an undetectable viral load that was less than 50 copies/mL for at least a year, changed ART to dolutegravir plus 3TC. Everyone in the study was doing well before switching. This was defined as having undetectable viral load on treatment for at least the previous year. People were not only older than those in the PADDLE study (average age was 59) but they had a long HIV treatment history, having been on ART for an average of almost 18 years. What is unusual -- and a significant caution -- is that seven people had already used another integrase inhibitor (raltegravir) and eight had history of drug resistance to 3TC.
Over 24 weeks, viral load remained <20 copies/mL in all participants, with one blip at 52 copies/mL. Tolerability was also good, although two people changed back to their pre-switch combination because of fatigue with dolutegravir + 3TC.
A third study -- also from a French group -- reported on 31 people who were using dolutegravir as part of dual therapy with a range of other drugs but only three people used 3TC. As this third study also included 21 people using dolutegravir monotherapy, these results are described below with the single drug studies.4
Although the results of dual therapy studies were very positive, several studies went a step further. Three studies at EACS showed results from using dolutegravir as a single HIV drug, with a fourth study presented at a meeting linked to the main conference.
The first of these was an oral presentation of a Spanish study in which 33 people who were on stable treatment, having been undetectable viral load for an average of eight years. These were people with a long and complex history of treatment, but with no evidence of integrase inhibitor resistance and all participants switched to dolutegravir monotherapy.
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