HIV treatment for over 60s – switching drugs could improve bone and kidney health
Switching people over 60 away from a tenofovir disoproxil fumarate-containing regimen results in better bone and kidney-health related outcomes.
Switching from an antiretroviral treatment (ART) regimen containing tenofovir disoproxil fumarate (TDF) to a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (ECETA) can improve bone density and kidney safety in those aged 60 and above, a new study finds.
Due to improvements in antiretroviral treatment (ART), an increasing number of people living with HIV are ageing. In the USA, for example, 47% of people living with HIV are aged 50 or above, while global estimates suggest that over 50s now account for 13% of the total adult population of people living with HIV – equivalent to around 4.2 million people.
In previous studies, TDF regimens have been associated with bone and kidney-related side effects that can result in severe illness. Older people on ART tend to experience more side effects than younger people and this, coupled with older people’s general vulnerability to conditions such as osteoporosis, means it is important to examine the effects of specific ART regimens on this age group. Despite this, older people living with HIV are usually underrepresented in clinical trials.
The study, the first Phase III trial of any HIV-combination ART involving people aged 60 and above, ran between 2015 and 2018 in 36 European clinics. Its purpose was to examine whether an ECETA regimen is less damaging to bone and kidney health for this age group than a TDF regimen, while maintaining viral suppression.
A total of 167 people aged 60 and above who were already on TDF and virally suppressed were randomly assigned to either stay on that regimen (56 participants) or switch to the ECETA alternative (111 participants). Most participants were male and white and the mean age was 66.
Significantly improved bone mineral density was observed among those who had switched regimens after six-months (24 weeks), something that continued to improve as the study went on. In contrast, declines in bone mineral density were observed among those on TDF regimen.
After 12 months (48 weeks), the mean percentage change in spine bone density among those in the ECETA group was 2.24% from baseline, compared to −0.10% in the TDF group, equating to a difference of 2.43%. Similarly, the difference at 48 weeks between hipbone density was 1.33% from baseline in the ECETA group and −0.73% in the TDF group, a difference of 2.04%.
Viral suppression was maintained among those that switched regimens and moderate increases in CD4 cell counts were also observed. Improvements in renal biomarkers, which indicate kidney health, were also found among those on ECETA regimen.
Due to the number of drugs used in the ECETA regimen there was a concern that people could be more vulnerable to side effects caused by adverse drug–drug interactions if they were taking medication for other conditions. This issue is particularly relevant for older people who may be more likely to be on treatment for other health issues than younger people. However, the study found switching to ECETA was generally well tolerated in participants, a substantial proportion of whom were taking other medication alongside their HIV treatment.
Although no serious treatment-related side effects were observed in either group, some milder side effects were reported in both. The most common side effects in the ECETA group were sore throats (12 participants or 11%), back pain (nine participants or 8%), and diarrhoea (eight participants or 7%). The most common side effects in the TDF group were bronchitis (six participants or 11%), vitamin D deficiency (four participants or 7%), and joint pain (four participants or 7%).
The finding are generally consistent with other studies of phase 3 trials of ECETA versus elvitegravir, cobicistat, emtricitabine, and TDF. These trials also showed similar efficacy but significantly fewer renal and bone effects with ECETA compared with those TDF-containing regimen.