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Safety and effectiveness of dolutegravir + 3TC in people with HIV aged 65 and older

Thanks to the tremendous benefits of HIV treatment (ART), researchers are finding that more people with HIV who are on ART are living into their senior years. Projections from large studies suggest that many ART users will have a near-normal life expectancy.

As more people with HIV grow older thanks to ART, more research is needed with older people. This research is vital because the metabolism of older people is slower than in younger people and older people tend to have other health conditions—high blood pressure, diabetes, high cholesterol—that require treatment. The drugs used to treat these other health conditions may interact with HIV treatment.

A team of researchers at the University of Bologna in Italy has reviewed medical records of 72 people with HIV whose average age was 69. Participants had been living with HIV for many years and were taking ART regimens that consisted of three or four drugs. These regimens suppressed their HIV to an undetectable level. All participants were switched to a combination of two anti-HIV drugs: dolutegravir + 3TC (sold in a pill called Dovato). Researchers then collected laboratory and clinical data for one year afterward.

In general, researchers found that the combination was well tolerated and when side effects did occur, they were mild and temporary. Three people developed virological failure—in all cases less than 2,000 copies/mL. Analysis of their blood samples did not reveal HIV that was resistant to dolutegravir or 3TC. Doctors reported that all three people did not take their pills as directed. However, they were given alternative regimens and subsequently re-suppressed HIV. The remaining participants all maintained a suppressed viral load (in this case, less than 20 copies/mL).

The present study was not a randomized clinical trial. However, the results are likely similar to what occurs in the everyday world of an HIV clinic (outside of the setting of a clinical trial). The results of the Italian study, though relatively small, are encouraging. A larger analysis from an observational study also in Italy and data from randomized clinical trials involving people over the age of 50 are summarized at the end of this report. Their results are all in alignment.

Study details

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

  • 82% men and 18% women
  • age – 69 years
  • lowest-ever CD4+ count – 184 cells/mm3
  • current CD4+ count – 503 cells/mm3
  • time since HIV diagnosis – 22 years
  • duration of ART regimen prior to switching to dolutegravir + 3TC – 7 years
  • viral load – prior to switching to dolutegravir + 3TC, all participants had a suppressed viral load (which the researchers defined as less than 20 copies/mL due to the assay in use at the study centre)
  • comorbidities – nearly 90% of participants had other health conditions, including high blood pressure, osteoporosis, type 2 diabetes, heart disease
  • weight – on average, participants weighed 68 kg and their body mass index (BMI) was 23 kg/m2

Common reasons for switching to dolutegravir + 3TC included the following:

  • avoiding interactions between ART and medicines used to treat comorbidities
  • wanting to simplify ART
  • reducing side effects from the current regimen

Note that participants were not supposed to have any of the following:

  • a history of virological failure
  • resistance testing that revealed the presence of HIV that was resistant to dolutegravir or 3TC
  • hepatitis B virus (HBV) coinfection
  • a diagnosis of alcohol or substance use disorder
  • kidney injury
  • liver injury

Prior to switching to dolutegravir + 3TC, drugs that participants took as part of their HIV treatment that were causing problems included the following:

  • elvitegravir + cobicistat (in Genvoya and Stribild)
  • efavirenz (in Atripla and generic formulations)
  • darunavir + cobicistat (in Prezcobix)
  • rilpivirine (Edurant and in Odefsey); rilpivirine is also found in another pill called Juluca (dolutegravir + rilpivirine) but participants were not taking this

Some of the side effects from their previous ART regimens that participants developed included the following:

  • high levels of cholesterol and triglycerides in the blood
  • unspecified gastrointestinal symptoms
  • a significant increase in weight

Results

Viral suppression

All participants had an undetectable viral load (less than 20 copies/mL) just prior to switching regimens. Subsequently, all but three participants maintained viral suppression.

Three participants developed a persistently detectable viral load between 600 to 1,800 copies/mL. Resistance testing revealed that none of the three people developed HIV that was resistant to dolutegravir or 3TC. Upon questioning, the three people disclosed that they had not been adherent to ART; the reasons for non-adherence were not disclosed by the research team. Although participants in the study were not supposed to have a history of virological failure, researchers stated that two of these three people disclosed past episodes of virological failure with previous regimens.

Two of these three people were then given their previous regimen: in one case this was darunavir + cobicistat and two nucleoside analogues; in the other case, the treatment was Odefsey. The third participant was given Triumeq (a pill containing dolutegravir + 3TC and abacavir). All three people subsequently re-suppressed their HIV.

Side effects

According to the researchers, none of the participants developed serious side effects. However, three people discontinued dolutegravir + 3TC because of problems sleeping (two people) and headache (one person).

Other people reported the following adverse events, but these were graded as mild to moderate and resolved within a couple of weeks:

  • sleeping problems – 11%
  • diarrhea – 10%
  • nausea and loss of appetite – 6%
  • headache – 6%
  • depression – 4%

Lipids and weight

Researchers reported that at the 12th month of the study, concentrations of fatty substances in the blood—total cholesterol, LDL cholesterol and triglycerides—all fell significantly. There was no change to HDL cholesterol.

There was a slight and non-significant increase in weight and BMI by the 12th month of the study. Weight increased by 0.67 kg and BMI increased by one-third of a point (0.31 kg/m2).

Drug interactions

Researchers reported that the risk of drug interactions decreased “considerably” after participants switched to dolutegravir + 3TC. In 12 people, it was possible that an interaction between metformin (a drug used to help control blood sugar levels) and dolutegravir occurred during the study; however, the researchers are not certain about this. In general, published reports suggest that if such an interaction occurs, it can be dealt with by prescribing a lower dose of metformin.

Bear in mind

The present study was not a randomized clinical trial. However, it does provide useful information on some older people who used dolutegravir + 3TC.

A larger Italian study, also observational in design, which was published two years ago analysed data from 822 people whose average age was 70 years. Participants were taking the following integrase inhibitors:

  • a dolutegravir-based regimen – 483 people
  • a raltegravir-based (Isentress) regimen – 243 people
  • Genvoya – 96 people

Rates of discontinuation were lowest for dolutegravir-based regimens and no cases of virological failure occurred.

The manufacturer of Dovato, ViiV Healthcare, has collected data from four randomized controlled trials and re-analysed these studies to assess the effects of dolutegravir + 3TC (or other combinations of dolutegravir) in people aged 50 and older. ViiV focused on 242 people with HIV who were virologically suppressed. According to ViiV, people aged 50 and older had high and similar rates of viral suppression as younger people. Rates of side effects in older people were similar to those seen in younger people. A total of 14 people aged 65 and older were given dolutegravir + 3TC in two of the trials (code-named Tango and Salsa); rates of virological suppression and side effects were similar to those seen in younger people.

—Sean R. Hosein

REFERENCES:

  1. Calza L, Colangeli V, Legnani G, et al. Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people living with HIV-1 aged over 65 years. AIDS Research and Human Retroviruses. 2023; in press.
  2. Focà E, Calcagno A, Calza S, et al. Durability of Integrase STrand Inhibitor (InSTI)-based regimen in geriatric people living with HIV in the GEPPO cohort. PLoS One. 2021 Oct 13;16(10):e0258533. 
  3. Prakash M, Grove R, Wynne BR, et al. 1267. Efficacy and safety of switching to DTG/3TC in virologically suppressed PLWH by age, including those aged ≥65 years: Pooled results from the TANGO and SALSA studies. Open Forum Infectious Diseases. 2022 Dec 15;9(Suppl 2):ofac492.1098.