Gaining weight after switching to a brand new antiretroviral mixture is frequent, particularly after switching from efavirenz or the older formulation of tenofovir, however most weight achieve is modest and happens within the first 12 months after switching, a overview of 12 massive scientific trials exhibits.
The outcomes counsel that some older antiretrovirals could have a weight-suppressive impact, which can clarify among the weight achieve seen after switching to a brand new routine. The findings are revealed within the journal AIDS.
Weight gain after starting antiretroviral treatment has been observed in numerous clinical trials. Beforehand untreated individuals are extra prone to achieve weight after beginning regimens that include the nucleotide reverse transcriptase inhibitor tenofovir alafenamide (TAF) or the integrase inhibitors bictegravir (in Biktarvy) or dolutegravir (Tivicay, additionally in Triumeq and Dovato).
Nonetheless, antiretroviral medicine usually are not the one issue related to weight achieve in individuals beginning therapy. A decrease CD4 depend, Black race, feminine intercourse, and baseline weight are additionally related to weight achieve, and it isn’t clear how a lot every of those components contributes to the chance of weight achieve, or how they could result in weight achieve. Among the weight gained after beginning therapy could also be a ‘return to well being’ impact, particularly in individuals with extra superior HIV illness or decrease physique weight.
To disentangle the consequences of medicines and particular person components, some researchers have suggested taking a look at research of people that change from one routine to a different, as this group of individuals will have already got skilled any ‘return to well being’ weight achieve on their first antiretroviral routine.
To analyze this query, a global group of researchers analysed adjustments in weight in 12 potential randomised research through which individuals switched to at the least one new antiretroviral drug. All research individuals had viral hundreds under 50 copies/ml for at the least three months on the time of switching.
All of the research have been sponsored by Gilead Sciences. 4 research investigated switching to Genvoya (elvitegravir, cobicistat, emtricitabine and TAF), 4 research investigated switching to Biktarvy (bictegravir, emtricitabine and TAF) and two research to Odefsey (rilpivirine, emtricitabine and TAF). Two research in contrast staying on a routine containing TDF to switching to 1 containing TAF. There was appreciable variety in individuals’ prior regimens.
The pooled evaluation included 4,166 individuals who switched therapy and three,150 who continued their current routine. Members contributed 11,456 person-years of follow-up time in seven research lasting 96 weeks and 5 research lasting 48 weeks.
Inhabitants traits have been related in most research – roughly 85% to 90% male, greater than two-thirds White and at the least two-thirds aged 35 or over – besides for 2 trials. One research of Biktarvy recruited solely girls and 37% of individuals have been Black, whereas a research of Genvoya recruited individuals over the age of 60 solely.
Weight was measured each 12 weeks within the scientific trials. The evaluation of the pooled trial knowledge confirmed that individuals who switched therapy gained a median of 1.6kg (IQR -0.5, +4kg) by week 48 and 2kg (IQR -0.5, +5.2kg) by week 96. Those that remained on their current routine gained 0.4kg (IQR -1.8, +2.4kg) by week 48 and 0.5kg (-1.9, +3.1kg) by week 96.
The quantity of weight gained by most individuals was modest and is unlikely to have any long-term influence on well being.
The proportion of individuals who have been overweight (physique mass index of 30 or above) elevated from 21% within the change group to 25% after 96 weeks however remained the identical (21%) in those that didn’t change.
Being underweight or regular weight at baseline was related to higher weight achieve (+0.8kg) than being overweight. Folks aged 35 years or much less gained extra weight than older individuals (+0.4kg). No different baseline components have been related to weight achieve.
When the associations between particular antiretrovirals and weight achieve have been analysed, the next switches have been related to vital weight achieve when in comparison with staying on the present routine:
- Switching from efavirenz to rilpivirine
- Switching from efavirenz to elvitegravir/cobicistat
- Switching from elvitegravir/cobicistat to bictegravir
- Switching from tenofovir (TDF) to tenofovir alafenamide (TAF)
- Switching from abacavir to TAF
“It stays unsure whether or not that is because of the lack of a weight suppressive impact of prior regimens or a weight achieve impact of the newer routine.”
However switching from rilpivirine to elvitegravir/cobicistat was related to vital weight reduction when in comparison with staying on the present routine.
Weight achieve of at the least 10% occurred in just below 5 % of individuals. After controlling for baseline traits, logistic regression evaluation confirmed that weight achieve of at the least 10% was related to being underweight or regular weight at research entry or being aged 35 or below. When the evaluation additionally included therapy switches, individuals who switched from efavirenz to rilpivirine or to elvitegravir/cobicistat, or from TDF to TAF, have been discovered to be at increased threat of gaining at the least 10% in weight.
The investigators additionally regarded on the interplay between race and intercourse. Ladies gained barely extra weight than males (+0.3kg, p=0.0046), with no distinction by race. Black males gained extra weight than non-Black males (0.3kg, p=0.041) and non-Black females gained extra weight than non-Black males (+0.5kg, p=0.013).
Substantial weight achieve (>10%) was not related to metabolic adjustments aside from a small discount in HDL levels of cholesterol.
“Our outcomes reveal that modest weight achieve is frequent after ART change and is correlated extra strongly with baseline routine, particularly change off of TDF or EFV, than with sex-, race- or HIV-related components,” conclude the investigators.
“It stays unsure whether or not that is because of the lack of a weight suppressive impact of prior regimens or a weight achieve impact of the newer routine. A greater understanding of the underlying organic mechanisms and the scientific implications are wanted to totally perceive these observations.”