People with HIV who switch from taking tenofovir disoproxil fumarate (TDF) to taking tenofovir alafenamide (TAF) subsequently gain a considerable amount of weight regardless of the other antiretrovirals (ARVs) in their regimen, the National AIDS Treatment Advocacy Project reports.
However, in a recent study presented at the International AIDS Conference that is being held virtually this week, nine months after the switch, people’s weight tended to stabilize or even decline during the subsequent nine months, depending on the other two ARVs in their regimen.
TAF is an updated version of TDF, which research indicates is less toxic to the bones and kidneys. However, more recent findings have indicated that switching to TAF is associated with weight gain and rising cholesterol. This may be due in part to TDF, but not TAF, having a suppressive effect on body weight.
TDF is sold as an individual tablet under the brand name Viread and is included in the single-tablet regimens Atripla, Complera, Delstrigo, Stribild, Symfi and Symfi Lo. It is also included in the combination tablets Cimduo, Temixys and Truvada.
TAF is approved as an individual tablet only for the treatment of hepatitis B virus and is sold under the brand name Vemlidy. It is included in the HIV single-tablet regimens Biktarvy, Genvoya, Odefsey and Symtuza. It is also included in the combination tablet Descovy.
Descovy and Truvada are each also approved for use as HIV pre-exposure prophylaxis (PrEP).
The new weight gain findings come from an analysis of the OPERA cohort, which includes more than 115,000 people receiving HIV-related medical care in 65 U.S. cities. The investigators included in their analysis people who were taking a three-ARV regimen that included TDF who had had two or more consecutive viral load test results below 200 at the time they switched to TAF.
The study authors adjusted their data to account for differences between the cohort members in age, sex, race, body mass index (BMI), CD4 count, endocrine disorders (such as diabetes) and other medications that could affect weight.
The analysis included 1,454 people who were taking a non-nucleoside reverse transcriptase inhibitor (NNRTI) and stayed on that drug when they switched from TDF to TAF; 747 who kept taking a boosted protease inhibitor; 3,288 who kept taking an integrase inhibitor; and 1,430 who switched from an NNRTI or a protease inhibitor to an integrase inhibitor.
The median age in these four groups ranged from 45 to 51. Fifteen percent to 21% were women; 37% to 41% were Black and 24% to 26% were Latino. The median BMI was 26 to 27 (a BMI of 25 to 29.9 indicates an individual is overweight). About one in four individuals had an endocrine disorder, and a similar proportion took non-ARV medications that could affect their weight.
Those who only switched from TDF to TAF gained 4.4 to 5.8 pounds during the subsequent nine months, but then their weight leveled off. However, those taking an integrase inhibitor gained 0.7 pounds during the second nine-month period after the switch.
When parsing the weight gain among those who stayed on their integrase inhibitor according to which drug in this class they were taking, the study authors found that during the first nine months, the weight gain was highest among those taking cobicistat-boosted elvitegravir (5.5 pounds), which is included with TDF in Stribild. Weight gain was next highest among those taking dolutegravir (5.3 pounds), which is sold as an individual tablet under the brand name Tivicay, followed by raltegravir (4.0 pounds), which is sold as an individual tablet under the brand name Isentress.
During the second nine months, the only people in the integrase inhibitor–maintaining group who experienced statistically significant weight gain were those on boosted elvitegravir, who gained 2.2 pounds. The weight of those taking either of the other two integrase inhibitors stabilized.
Among those who switched from an NNRTI or a protease inhibitor to an integrase inhibitor, switching to bictegravir, which is included with TAF in Biktarvy, was tied to greater weight gain during the first nine months, at 9.9 pounds. However, those in the bictegravir group were the only ones who lost weight during the second nine months, shedding 22.0 pounds. During the first nine months, those who switched to boosted elvitegravir gained 5.6 pounds and those who switched to dolutegravir gained 6.8 pounds, after which both groups saw their weight stabilize during the second nine months.
The study authors concluded that switching from TDF to TAF independently drives up weight regardless of whether there is a change in the other ARVs in an individual’s regimen.
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