In the Journals

Isentress causes less bone density loss than PIs

HIV patients who received Isentress with Truvada maintained greater bone density than those who were prescribed protease inhibitors, according to research in The Journal of Infectious Diseases.

“Osteoporosis is common in human immunodeficiency virus-infected populations, and emerging evidence suggests that fracture risk is higher in HIV-infected persons compared with age-matched, HIV-uninfected controls,” Todd T. Brown, MD, PhD, of Johns Hopkins University, and colleagues wrote “The first 48 weeks after antiretroviral therapy initiation have consistently been associated with a bone mineral density loss of approximately 2% to 6%, which does not return to baseline during continued treatment. The magnitude of this BMD loss is dependent in part on the specific medications used.”

Brown and colleagues conducted a randomized controlled study of 328 ART-naive participants aged 18 years and older with an HIV RNA load of at least 1,000 copies/mL, enrolled from the AIDS Clinical Trials Group in the United States.

Todd T. Brown

All patients were assigned Truvada (tenofovir disoproxil fumarate with emtricitabine, Gilead Sciences) plus one of three drug combinations:

  • Reyataz (atazanavir, Bristol-Myers Squibb) and Norvir (ritonavir, AbbVie), or ATV/r;
  • Prezista (darunavir, Janssen) with ritonavir), referred to as DRV/r; or
  • Isentress (raltegravir, Merck), or RAL.

Patients were studied over 96 weeks to determine changes in lumber spine and total hip BMD, according to the researchers.

Mean percentage of bone density loss was similar in the protease inhibitor (PI) arms of the study: spine, –4% in the ATV/r group vs. –3.6% the DRV/r group; and hip, –3.9% in the ATV/r group compared with –3.4% in the DRV/r group. However BMD loss was greater in the combined PI arms than the RAL arm: spine, –3.8% compared with –1.8% (P < .001) and hip, –3.7% vs. –2.4% (P = .005).

Total body BMD showed a significant decrease across all treatment groups (P = .001), although there was a marked difference between PIs (ATV/r, –2.9% vs. DRV/r, –1.6%; P = .001) as well as between the ATV/r and RAL arms (–2.9% vs 1.7%; P = .004). The DRV/r and RAL arms were nearly identical. The researchers said the noticeable difference between results with regard to total body BMD may be due to the different composition of bones in the body, which are much more cortical (80%) in total than either the spine (20%) or the hip (50%).

“For HIV-positive patients initiating antiretroviral therapy who also have osteoporosis or are otherwise at increased risk of fracture, avoiding protease inhibitors in favor of integrase inhibitors is a good strategy to preserve bone health,” Brown told Infectious Disease News. “This study also adds to the growing literature showing bone-neutral effects of integrase inhibitors, which also may be safer for patients with bone problems already on antiretroviral therapy who are looking to switch to a more bone-friendly regimen.” – by David Jwanier

Disclosure: Brown reports that he has served as a consultant for Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck and ViiV Healthcare, and has received research funding from GlaxoSmithKline and Merck. Please see the full study for a list of all other authors’ relevant financial disclosures.

HIV patients who received Isentress with Truvada maintained greater bone density than those who were prescribed protease inhibitors, according to research in The Journal of Infectious Diseases.

“Osteoporosis is common in human immunodeficiency virus-infected populations, and emerging evidence suggests that fracture risk is higher in HIV-infected persons compared with age-matched, HIV-uninfected controls,” Todd T. Brown, MD, PhD, of Johns Hopkins University, and colleagues wrote “The first 48 weeks after antiretroviral therapy initiation have consistently been associated with a bone mineral density loss of approximately 2% to 6%, which does not return to baseline during continued treatment. The magnitude of this BMD loss is dependent in part on the specific medications used.”

Brown and colleagues conducted a randomized controlled study of 328 ART-naive participants aged 18 years and older with an HIV RNA load of at least 1,000 copies/mL, enrolled from the AIDS Clinical Trials Group in the United States.

Todd T. Brown

All patients were assigned Truvada (tenofovir disoproxil fumarate with emtricitabine, Gilead Sciences) plus one of three drug combinations:

  • Reyataz (atazanavir, Bristol-Myers Squibb) and Norvir (ritonavir, AbbVie), or ATV/r;
  • Prezista (darunavir, Janssen) with ritonavir), referred to as DRV/r; or
  • Isentress (raltegravir, Merck), or RAL.

Patients were studied over 96 weeks to determine changes in lumber spine and total hip BMD, according to the researchers.

Mean percentage of bone density loss was similar in the protease inhibitor (PI) arms of the study: spine, –4% in the ATV/r group vs. –3.6% the DRV/r group; and hip, –3.9% in the ATV/r group compared with –3.4% in the DRV/r group. However BMD loss was greater in the combined PI arms than the RAL arm: spine, –3.8% compared with –1.8% (P < .001) and hip, –3.7% vs. –2.4% (P = .005).

Total body BMD showed a significant decrease across all treatment groups (P = .001), although there was a marked difference between PIs (ATV/r, –2.9% vs. DRV/r, –1.6%; P = .001) as well as between the ATV/r and RAL arms (–2.9% vs 1.7%; P = .004). The DRV/r and RAL arms were nearly identical. The researchers said the noticeable difference between results with regard to total body BMD may be due to the different composition of bones in the body, which are much more cortical (80%) in total than either the spine (20%) or the hip (50%).

“For HIV-positive patients initiating antiretroviral therapy who also have osteoporosis or are otherwise at increased risk of fracture, avoiding protease inhibitors in favor of integrase inhibitors is a good strategy to preserve bone health,” Brown told Infectious Disease News. “This study also adds to the growing literature showing bone-neutral effects of integrase inhibitors, which also may be safer for patients with bone problems already on antiretroviral therapy who are looking to switch to a more bone-friendly regimen.” – by David Jwanier

Disclosure: Brown reports that he has served as a consultant for Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck and ViiV Healthcare, and has received research funding from GlaxoSmithKline and Merck. Please see the full study for a list of all other authors’ relevant financial disclosures.