Prior research have proven that folks dwelling with HIV who begin or swap to an antiretroviral routine containing tenofovir alafenamide (TAF), particularly together with an integrase inhibitor, are more likely to acquire weight. Now, new analysis reveals that switching—or switching again— to the older tenofovir disoproxil fumarate (TDF) might assist folks drop some weight.
Lately, there was rising concern about weight acquire after beginning antiretroviral therapy or switching to a brand new routine. Ladies—Black ladies particularly—are extra liable to placing on kilos.
Weight acquire within the context of HIV therapy just isn’t absolutely understood. A number of the largest will increase have been seen in individuals who begin potent integrase inhibitors, corresponding to dolutegravir (offered alone as Tivicay and a element of the Triumeq, Dovato and Juluca single-tablet regimens). TAF, the newer type of tenofovir in Descovy and in single-tablet regimens corresponding to Biktarvy and Symtuza, has been linked to extra weight acquire than TDF, the older type in Truvada and n mixture drugs together with Atripla, Complera and Delstrigo. (Click on right here to study extra in regards to the variations between TAF and TDF.)
For instance, within the ADVANCE trial in South Africa, which in contrast three first-line antiretroviral regimens, members randomly assigned to start out on dolutegravir, TAF and emtricitabine gained extra weight than those that used dolutegravir, TDF and emtricitabine, who in flip gained greater than those that used efavirenz, TDF and emtricitabine. Last outcomes at 192 weeks, offered eventually summer time’s Worldwide AIDS Convention, confirmed that after practically 4 years, folks within the three therapy teams gained about 19 kilos, 13 kilos and seven kilos, respectively, with ladies gaining greater than males. All three regimens labored equally properly for suppressing HIV.
Amongst folks already on therapy with an undetectable viral load, a research of practically 7,000 members within the U.S. OPERA cohort discovered that those that switched from TDF to TAF skilled “pronounced weight acquire,” particularly if additionally they switched to an integrase inhibitor on the identical time. Likewise, an evaluation of greater than 700 individuals who modified regimens within the U.S. HIV Outpatient Research discovered that those that switched to an integrase inhibitor or TAF noticed will increase of their physique mass index. As reported on the 2022 Convention on Retroviruses and Opportunistic Infections and within the Journal of Acquired Immune Deficiency Syndrome, weight acquire was biggest in the course of the first eight months, principally related to integrase inhibitor use, after which there was a extra gradual enhance, largely attributed to TAF use.
However integrase inhibitors and TAF will not be fully accountable for added kilos. TDF can result in lowered ldl cholesterol and triglyceride ranges and both a small quantity of weight reduction or absence of anticipated weight acquire over time. This has been seen in HIV-negative folks taking Truvada for pe-exposure prophylaxis (PrEP) in addition to HIV-positive folks utilizing TDF-containing therapy regimens.
TAF lacks this weight-suppressing impact, so individuals who swap from TDF to TAF—as is commonly beneficial to keep away from the kidney and bone negative effects of TDF—might expertise rising blood fats ranges and weight acquire. However weight acquire has additionally been seen in individuals who swap to a TDF-sparing routine that doesn’t include TAF. And a few analysis means that different antiretrovirals, together with efavirenz, may additionally inhibit weight acquire.
Switching to TDF
No matter its trigger, undesirable weight acquire isn’t just a beauty or shallowness situation. Extra weight—particularly the buildup of visceral stomach fats deep inside the stomach—raises the danger of heart problems, diabetes, fatty liver illness, a number of forms of most cancers and different well being issues.
To handle undesirable weight acquire, specialists advocate way of life modifications corresponding to consuming a wholesome plant-based eating regimen, rising bodily exercise and getting sufficient sleep. However many individuals are unable to drop some weight by eating regimen and train alone, elevating the query of whether or not switching antiretrovirals would possibly assist.
As reported in Scientific Infectious Illnesses, Francois Venter, MD, PhD, of the College of the Witwatersrand in Johannesburg, and colleagues analyzed weight and metabolic modifications amongst folks within the ADVANCE trial who switched to a brand new routine.
As described above, greater than 1,000 ADVANCE members had been randomized to start out therapy with both dolutegravir, TAF and emtricitabine; dolutegravir, TDF and emtricitabine; or efavirenz, TDF and emtricitabine. After practically 4 years on their assigned preliminary routine, they switched to dolutegravir, TDF and lamivudine when nationwide therapy tips modified.
Venter’s crew centered on 172 folks in Johannesburg who joined a follow-up sub-study dubbed CHARACTERISE. After one yr, those that switched from dolutegravir, TAF and emtricitabine or from efavirenz, TDF and emtricitabine to the brand new routine noticed notable reductions in weight, blood lipids and blood sugar.
Ladies who switched from dolutegravir, TAF and emtricitabine to dolutegravir, TDF and lamivudine misplaced a median 3.5 kilos, however the males misplaced solely 0.4 kilos. Amongst members who switched from efavirenz, TDF and emtricitabine to the brand new routine, the ladies misplaced a median 6.4 kilos, whereas the boys misplaced a median 5.1 kilos. Amongst those that switched from dolutegravir, TDF and emtricitabine to dolutegravir, TDF and lamivudine—a really related routine—neither the ladies nor the boys noticed a big change in weight.
Individuals who switched from dolutegravir, TAF and emtricitabine to dolutegravir, TDF and lamivudine confirmed important declines in complete ldl cholesterol, low-density lipoprotein (LDL, or dangerous ldl cholesterol), triglycerides, blood glucose and HbA1C, one other measure of blood sugar. Those that switched from efavirenz, TDF and emtricitabine to the brand new routine noticed important drops in complete ldl cholesterol, LDL, high-density lipoprotein (HDL, or good ldl cholesterol), triglycerides and HbA1C. Lastly, individuals who switched from dolutegravir, TDF and emtricitabine to dolutegravir, TDF and lamivudine noticed a rise in complete ldl cholesterol however no important modifications within the different measures.
In a associated research reported within the journal AIDS, Jussi Sutinen, MD, PhD, of the College of Helsinki, and colleagues seemed on the results of switching from TAF to TDF, whereas holding different antiretrovirals and lipid-lowering drugs unchanged, in a retrospective chart overview that included practically 300 folks with HIV in Finland, most of whom had been white males.
Among the many 146 individuals who switched from TAF to TDF, physique weight remained steady after two years, whereas it rose by about 3 kilos on common in a matched group of people that stayed on TAF. Whole ldl cholesterol and LDL every declined by about 12% within the swap group after one yr. However HDL additionally decreased, so the overall cholesterol-to-HDL ratio—an indicator of cardiovascular threat—didn’t change. No important modifications had been noticed within the management group that didn’t swap. What’s extra, the atherosclerotic heart problems threat rating decreased barely within the swap group (from 6.3% to six.0%) however rose within the management group (from 8.4% to 9.1%).
Taken collectively, these research counsel that some folks would possibly profit from switching, or switching again, from TAF to TDF. However the benefits of doing so should be weighed in opposition to the danger of impaired kidney perform and bone loss because of TDF, negative effects that TAF doesn’t share. The findings underscore the significance of individualized therapy that takes under consideration comorbidities and different elements that would increase the danger of damaging outcomes.
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