TreatmentUpdate
212

January 2016 

A study from Barcelona about switching to dolutegravir monotherapy

Doctors in Barcelona, Spain, enrolled HIV-positive participants taking anti-HIV therapy whose viral load in the blood was less than 50 copies/mL. No participant had a history of resistance to integrase inhibitors. Due to the risky nature of the study—therapy with just one drug—researchers were careful to enroll only people who were generally having issues with their current regimen, such as the following, and who might need a simplified regimen:

  • drug-related side effects
  • other illnesses (co-morbidities) that were difficult to manage because of interactions between medicines
  • HIV that was resistant to many therapies and resulted in doctors prescribing complex and burdensome regimens

Researchers reported results from 33 participants who were switched from some other therapy (in some cases monotherapy with darunavir [Prezista] + ritonavir [Norvir]). Overall, the results suggest that switching to dolutegravir monotherapy may be useful in some people, at least in the short term.

Study details

The average profile of participants upon entering the study was as follows:

  • age – 56 years
  • 45% men, 55% women
  • years since HIV diagnosis – 19
  • history of AIDS-related infections/complications – 39%
  • CD4+ count – 600 cells/mm3
  • CD8+ count – 990 cells/mm3
  • HIV viral load – less than 37 copies/mL
  • years with an undetectable viral load – 8

Results

After 24 weeks of dolutegravir monotherapy, 32 out of 33 participants (97%) maintained an undetectable viral load. There were no significant changes in cell counts.

In one participant, doctors detected what they called “low-level virological failure” after four weeks in the study. That is, his viral load was 88 copies/mL. Another viral load test was subsequently requested and doctors found that it had increased to 155 copies/mL. We will provide more information about this case later.

Changes in other blood tests

Overall, after 24 weeks of dolutegravir monotherapy, researchers found that most participants had significant and favourable decreases in the following fatty substances in their blood:

  • triglycerides
  • total cholesterol

Other changes

The study doctors reported that the following occurred once participants switched to dolutegravir monotherapy:

  • no drug interactions between dolutegravir and medicines used to treat other conditions
  • nausea, vomiting and/or diarrhea, which was a problem for some participants prior to the study, “improved or disappeared in nine of 11 [affected participants]”
  • the risk of a heart attack declined
  • one participant with kidney injury had improvement

Adverse events

No participant stopped taking dolutegravir due to side effects.

Two participants had serious adverse events, as follows:

  • amputation of a foot due to complications stemming from diabetes
  • syphilis

However, none of these adverse events were caused by dolutegravir.

Focus on one case

The doctors noted that the man in whom dolutegravir monotherapy failed had a complex medical history.

At the time of the study he was 52 years old and had been HIV positive for 12 years. During that time he had been on 10 different regimens. One of these regimens contained the integrase inhibitor raltegravir (Isentress). His raltegravir-based regimen had failed though technicians were unable to find any HIV with mutations or changes in its genes suggesting raltegravir resistance.

Although he had a history of using multiple street drugs, the man stated that for the past two years he had not used these drugs. During the past two years he had been treated with darunavir (Prezista) + low-dose ritonavir (Norvir). Since the purpose of low-dose ritonavir in such a regimen is to boost and maintain high levels of darunavir, his therapy can be described as darunavir monotherapy. During the time he took darunavir monotherapy, his viral load was less than 37 copies/mL, suggesting good adherence.

The man was also taking many other medicines, including the following:

  • paliperidone (Invega Sustenna, Xeplion) – a long-acting drug used to treat bipolar disorder and schizophrenia
  • trazodone – an antidepressant
  • lorazepam (Ativan) – for management of anxiety
  • losartan – to treat his higher-than-normal blood pressure
  • pitavastatin (Livalo) – to help reduce his elevated cholesterol levels

When his viral load became detectable in the fourth week of the study, doctors advised him to raise his dose of dolutegravir to 50 mg twice daily, but he refused.

At the 24th week of the study, his viral load was detectable at 101 copies/mL. However, using conventional tests on his blood samples, technicians were unable to find HIV that was resistant to integrase inhibitors. When the tests used only in research settings were applied, they found that about 7% of the HIV-infected cells in his samples had a moderate degree of resistance to dolutegravir.

Bear in mind

In this non-randomized pilot study, researchers found that some treatment-experienced participants did not experience obvious harm and may even benefit when switching to dolutegravir monotherapy. However, as mentioned previously, this study was not randomized, was relatively small and ran for a relatively short time. Furthermore, participants were carefully selected. Treatment failure in the study occurred in one participant who had previously used raltegravir (and who also experienced treatment failure when that drug was used). As raltegravir is chemically related to dolutegravir, HIV that is resistant to raltegravir can also have some degree of resistance to dolutegravir (and elvitegravir, found in Stribild and Genvoya).

It is still early days for dolutegravir monotherapy and much additional research is required.

—Sean R. Hosein

REFERENCE:

Rojas J, Blanco JL, Lonca M, et al. Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression: a 24-week pilot study. 15th European AIDS Conference, 21-24 October 2015, Barcelona, Spain. Abstract LBPS 4/2.