June 22, 2016
Gains in peripheral or central fat did not differ through 96 weeks of treatment in antiretroviral-naive patients randomized to start raltegravir (Isentress) or a ritonavir (Norvir)-boosted protease inhibitor (PI). Lean body mass increases through 96 weeks proved significant in the raltegravir arm and the atazanavir (Reyataz)/ritonavir arm but not in the darunavir (Prezista)/ritonavir arm. This AIDS Clinical Trials Group (ACTG) analysis linked higher pretreatment viral load to greater gains in peripheral and central fat.
Fat distribution changes may follow initiation of treatment for chronic diseases including HIV infection. These sometimes disfiguring changes can impair self-image, affect antiretroviral adherence and predispose patients to cardiovascular disease. Treatment with thymidine nucleoside analogs largely explained peripheral fat atrophy with antiretroviral therapy. Central fat gains first attributed to PIs continue to affect patients starting non-PI regimens.
To compare fat changes in antiretroviral-naive adults starting the integrase inhibitor raltegravir or ritonavir-boosted atazanavir or darunavir, all with tenofovir/emtricitabine (TDF/FTC, Truvada), ACTG investigators used abdominal CT and whole body DXA scans in a subset of patients enrolled in ACTG protocol A5257. In the parent trial, virologic results proved similar with all three regimens, but tolerability was worse with atazanavir/ritonavir than with the other two regimens.
Through 96 weeks of treatment, body mass index rose by 3.8% to 4.7% across study arms with no significant difference between arms. Trunk fat increased by 18.0% across arms with no significant differences between the PI arms or between the combined PI arms and the raltegravir arm. Changes in visceral adipose tissue (VAT) reflected trunk fat gains. At week 96, limb fat increased by an average 13.4% across study arms with no significant differences between the PI arms or between the combined PI arms and the raltegravir arm. Changes in subcutaneous adipose tissue (SAT) mirrored limb fat gains.
Average lean body mass rose significantly through 96 weeks with atazanavir (2%) and raltegravir (2%) but did not increase significantly with darunavir (1.2%). Adjusted models offered some evidence of greater lean body mass gains with atazanavir than with darunavir (P = .05). Lean body mass change did not differ significantly between the combined PI arms and the raltegravir arm.
Multivariable analysis adjusted for age, sex, body mass index, viral load, CD4 count and race/ethnicity determined that higher pretreatment viral load was associated with greater gains in limb fat, VAT and lean body mass (P < .01). A pretreatment viral load above 100,000 copies/mL was associated with 2- to 3-fold gains in all fat depots through 96 weeks.
The ACTG investigators note that the peripheral fat gains in their study reflect prior analyses involving regimens without thymidine nucleoside analogs. They speculate that the increase in body mass index in these patients "surpasses what is expected from return-to-health and may have unfavorable consequences on health." The authors propose that the link between higher pretreatment viral load and greater fat gains could reflect persistence of HIV-infected macrophages in adipose tissue. Even with effective antiretroviral therapy, they surmise, "the size of the reservoir of fat macrophages is likely related to the severity of the initial infection and may be resistant to treatment with antiretrovirals."
In a 126-person analysis of the NEAT001/ANRS143 trial, participants randomized to raltegravir plus darunavir/ritonavir added more trunk fat through 96 weeks of treatment than participants randomized to TDF/FTC plus darunavir/ritonavir. Limb fat changes did not differ significantly between arms.
Mark Mascolini writes about HIV infection.
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