- Biktarvy, a complete treatment in a pill for people with HIV, has been approved for several years
- The data used for the approval of Biktarvy was from a trial with young and middle-aged adults
- Now a clinical trial has found it generally safe and effective in people aged 65 and older
Most industry-sponsored clinical trials of HIV treatment (ART) have enrolled young and middle-aged adults. However, as a group, people with HIV are now living longer thanks to ART, and a majority of this population in high-income countries is over the age of 50. Furthermore, some ART users are reaching their senior years.
As people age, their organs may not work as well as they used to and certain health conditions—such as elevated levels of cholesterol, diabetes and high blood pressure—arise. Consequently, older people tend to be prescribed medicines to help manage these conditions. These are important reasons why new medicines to treat HIV need to be tested in older people.
About Biktarvy
Biktarvy is the name of a pill containing three anti-HIV medicines:
- bictegravir
- TAF (tenofovir alafenamide)
- FTC (emtricitabine)
Biktarvy is a complete HIV treatment, and both TAF and FTC have activity against HIV and hepatitis B virus.
In previous clinical trials with adults under the age of 65, Biktarvy has been found to be generally safe and effective. Biktarvy is one of several regimens recommended by leading HIV treatment guidelines.
A clinical trial in older people
A team of researchers in Belgium, France, Italy, Spain and the UK recruited 86 people with HIV. All participants were 65 years or older. Prior to the Biktarvy study, they had been taking other combinations of ART and had all achieved a suppressed viral load (less than 50 copies/mL).
Once in the study, participants stopped taking their previous regimen and immediately switched to Biktarvy.
After 96 weeks of observation, CD4+ cell counts remained stable and virologic suppression was maintained by 74% of participants. In general, Biktarvy was safe and there were no significant changes to weight.
Study details
The average profile of participants upon study entry was as follows:
- age – 69 years (ranging between 65 and 80 years)
- 87% male, 13% female
- major ethno-racial groups: White – 80%; Hispanic 15%
- weight – 78 kg
- body mass index (BMI) – 27 kg/m2
- CD4+ count – 676 cells/mm3
- number of medicines taken for other health conditions – 3 (most were used to treat cardiovascular disease, heartburn, anxiety and/or depression)
Common pre-study regimens:
- Genvoya – a pill containing elvitegravir + cobicistat + TAF + FTC
- Odefsey – a pill containing rilpivirine + TAF + FTC
The study began in March 2018 and ended in mid-2020 at the height of the first wave of the COVID-19 pandemic.
Results – Safety
Eleven people (13%) reported an adverse event linked to the study medicines. These were uncommon and generally mild or moderate. Side effects were wide ranging—including headache, constipation or diarrhea, dizziness, muscle pain and insomnia. In clinical trials such side effects are usually temporary in most people who experience them.
Three people left the study prematurely because of the following side effects:
- abdominal discomfort
- weight gain
- irritability
- sleep problems
Two other people left the study because they were having difficulty withdrawing from alcohol and drug use.
Two people died during the study from the following causes:
- one person with a history of depressive illness was depressed during the study and died from self-harm
- one person died from pneumonia arising from COVID-19
Investigators determined that these deaths were not related to Biktarvy.
Effectiveness
Two years after entering the study, 64 out of 86 people (74%) had a suppressed viral load. The reason that this figure was less than 100% was mainly due to a large number of people not going to the study clinic to give their final blood sample. As mentioned earlier, the study ended during the first wave of the COVID-19 pandemic. At that time, there were lockdowns and there were no vaccines to reduce the risk of developing COVID-19. Furthermore, there was much fear and uncertainty about the risk and consequences of developing COVID-19. The pandemic also affected recruitment and retention of people in other clinical trials.
In standard analyses done by regulatory authorities, missing data points (such as when people do not return to the study clinic) are assumed to have an unsuccessful outcome. In this case, those people who did not return for their final assessments in time were, for the purposes of analysis, assumed to have a detectable viral load.
Among the 64 people who did return to the study clinic to have their final blood samples drawn, all had a viral load of less than 50 copies/mL. Among these 64 people, 59 had a viral load less than 20 copies/mL.
At the start of the study, 12 people had some degree of low-level resistance by HIV to treatment, usually to TAF or FTC. No new cases of drug-resistant HIV occurred during the study.
As mentioned earlier, CD4+ cell counts were stable.
Focus on weight
In the current era, studies have reported increases in body weight and BMI in ART users. In some cases, people have become overweight or obese. However, in the present study, the vast majority of participants experienced very modest weight gain (1 kg).
A study from Italy with older people used HIV regimens based on another drug called dolutegravir (Tivicay and in Dovato and Triumeq). That study also did not find significant weight gain. Dolutegravir is structurally similar to bictegravir (one of the drugs in Biktarvy). It is therefore possible that older people with HIV are less susceptible to significant increases in weight than younger people when using Biktarvy or dolutegravir-containing regimens.
Focus on Black people
The current study on Biktarvy had only one Black participant. However, another study from Gilead, code-named Braave, enrolled primarily people who were Black. In Braave, people changed their previous regimen for Biktarvy. On average, people gained about 1 kg while in that study.
Bear in mind
Overall, the findings from the present study are a good step forward and extend the safety and effectiveness of Biktarvy to older people. Further studies by all pharmaceutical companies are needed that include a range of subpopulations, including women, transgender people, people of colour and people who use drugs.
—Sean R. Hosein
Resources
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV – U.S. Department of Health and Human Services
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2022 Recommendations of the International Antiviral Society–USA Panel – International Antiviral Society-USA
EACS Guidelines – European AIDS Clinical Society
REFERENCES:
- Maggiolo F, Rizzardini G, Molina JM, et al. Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age. HIV Medicine. 2023 Jan;24(1):27-36.
- Guaraldi G, Calza S, Milic J, et al. Dolutegravir is not associated with weight gain in antiretroviral therapy experienced geriatric patients living with HIV. AIDS. 2021 May 1;35(6):939-945.
- Bansi-Matharu L, Phillips A, Oprea C, et al. Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium. Lancet HIV. 2021 Nov;8(11): e711-e722.
- Perna A, Carleo MA, Mascolo S, et al. Adipocyte differentiation of 3T3-L1 cells under TAF, TDF and INSTIs selective challenge: an in vitro model. AIDS. 2023; in press.
- Lake JE, Trevillyan J. Impact of integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV. Current Opinion in HIV/AIDS. 2021 May 1;16(3):148-151.
- Grabar S, Potard V, Piroth L, et al. Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort. Journal of Antimicrobial Chemotherapy. 2023; in press.