Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Taiwo, Babafemi; Chan, Ellen S.; Fichtenbaum, Carl J.; Ribaudo, Heather J.; Tsibris, Athe; Klingman, Karin L.; Eron, Joseph J.; Berzins, Baiba; Robertson, Kevin; Landay, Alan; Ofotokun, Igho; Brown, Todd T.; Martinez, I Duran; Kalayjian, Robert C.; Wilson, Cara C.; Acosta, Edward P.; Rusin, D.; Gonzales, Amy L.; Roman, Orlando; Melbourne, Kathy; Rooney, James F.; Reinhart, Alex; Baugh, Bryan; Qaqish, Roula B.; R., Jayvant, Heera; Napolitano, Laura A.; Walworth, Charles; Petropoulos, Christos J.; Davis, John D.; Hite, Mark; Seefried, E.; Benson, Constance A.; Lambert, Nina; Coleman, Karen J.; James, Tamara; Dill, Amy; Baer, Jenifer; Griesmer, Christine; Basler, Cathi; Bolívar, Héctor; Fischl, Margaret A.; Arduino, Roberto C.; Villamil, Aristoteles E.; Sha, Beverly E.; Green, Tondria; Jackson, Barry; Nicotera, Fred; Kim, Ge-Youl; Mark, Rodrieguez,; Luetkemeyer, Annie; Dwyer, Jay; Poethke, Pamela; Rana, Aadia; Miriam, Chicurel-Bayard,; Telfer, Megan; Dam, Cornelius Van; Lane, Timothy W.; Ofotokun, Ighovwerha; Palmore, Melody; Walton, Patricia; Williams, Cecilia; Santana, Jorge; Méndez, Olga; Tebas, Pablo; Thomas, Aleshia; Flynn, Teri; Sbrolla, Amy; Landovitz, Raphael J.; Vanessa, Cajahuaringa,; Dunaway, Shelia B.; Storey, S. S.; Wiggins, Ilene; Weiss, Andrea; Reirden, Daniel; Bernath, Hannah; Yin, Michael T.; Noel-Connor, Jolene; Kim, Rose; Smith, Yolanda R.; Sax, Paul E.; Keenan, Cheryl; Kumar, Princy; Timpone, Joseph; P., DubCrossed Dsign, Michael; Santos, Bartolo; Adams, M. Jacob; Hurley, Christine

doi:10.1093/cid/civ455

Cited by 45 publications

(43 citation statements)

References 38 publications

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“…Net differences in percentage change in BMD between groups were significant at 24 weeks at both the spine and hip (spine: −0.91%; p=0.001 and hip: −0.61%; p=0.001)[44**]. Further, in HIV, studies comparing TDF-containing ART and ART without TDF in ART-naïve HIV-infected individuals have consistently shown that ART without TDF leads to less BMD decline over the first 48 to 96 weeks of treatment[45*, 46] as well as less increase in bone turnover markers[47*, 48]. Last, in virologically suppressed, HIV-infected participants, switching from a TDF-containing regimen to an alternative NRTI or an NRTI-sparing regimen also leads to improvement in bone turnover markers, including sclerostin, a selective regulator of bone formation through the Wnt pathway[49*] and results in increase in BMD[50*].…”

Section: Introductionmentioning

confidence: 99%

Bone loss in HIV

Hileman

Eckard

McComsey

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of the review Because of antiretroviral therapy, people are living with HIV infection longer than ever before. As this patient group ages, it is expected that medical co-morbidities such as osteoporosis and fragility fractures will increase. The purpose of this review is to address the epidemiology and what is known regarding the pathogenesis of bone loss in people living with HIV infection with a focus on recently published literature. Recent findings HIV-infected individuals are at increased risk for low bone mineral density and bone fractures. The cause of bone loss in HIV is multifactorial including traditional risk factors some of which disproportionately affect HIV-infected individuals and alterations in bone metabolism due to antiretroviral therapy (ART), HIV viral proteins and chronic inflammation. Lifestyle modification, changing ART, calcium and vitamin D supplementation and pharmacologic treatment for osteoporosis may all be employed to abrogate bone loss in this patient group. Summary Clinicians should be aware of the contributors to bone loss in people living with HIV in order to recognize high risk individuals and to take appropriate steps to address modifiable risk factors to prevent future fracture.

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Section: Introductionmentioning

confidence: 99%

Bone loss in HIV

Hileman

Eckard

McComsey

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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“…The overall 60% lower bone resorption in the ZOL arm relative to the placebo arm and the corresponding 11% relative higher BMD at the lumbar spine observed with ZOL at 48 weeks are the largest reported effect sizes for any prophylactic intervention directed at ameliorating ART-induced bone loss. At 48 weeks, supplementation with vitamin D and calcium carbonate in treatment-naive, HIV-infected patients in a recent study resulted in a relative treatment difference in total hip BMD of 1.86% [23], while in the A5303 study, the use of a TDF-sparing ART regimen was associated with relative treatment differences in total hip and lumbar spine BMD of 0.89% and 1.47%, respectively [9].…”

Section: Discussionmentioning

confidence: 96%

A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

et al. 2016

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Background. Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives.Methods. In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints.Results. The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck.Conclusions. A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted.Clinical Trials Registration. NCT01228318.

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“…A5303 was a phase 2, prospective, double‐blind, placebo controlled, multicenter, 48‐week study of maraviroc 150 mg or tenofovir disoproxil fumarate (tenofovir) 300 mg, each plus darunavir/ritonavir 800/100 mg and emtricitabine 200 mg in participants infected with the R5‐tropic HIV‐1 (Taiwo et al., 2015). Participants were ART naïve adults (aged ≥18 years) recruited from 33 AIDS Clinical Trials Group (ACTG) and four Adolescent Trials Network study sites in the USA.…”

Section: Methodsmentioning

confidence: 99%

“…Participants were ART naïve adults (aged ≥18 years) recruited from 33 AIDS Clinical Trials Group (ACTG) and four Adolescent Trials Network study sites in the USA. Participants in A5303 were randomized in a 1:1 ratio and stratified by plasma HIV‐1 RNA < or ≥100,000 copies/ml and age <30 or ≥30 years (Taiwo et al., 2015). …”

Section: Methodsmentioning

confidence: 99%

Similar changes in neuropsychological functioning in english and spanish speaking HIV patients

et al. 2018

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ObjectivePrimary language has been reported to influence the results of neuropsychological (NP) testing. We sought to determine whether being a primary Spanish versus English speaker affects changes in neuropsychological evaluations in persons living with HIV.MethodData from 209 (188 English speakers and 21 Spanish speakers) ART‐naïve HIV‐infected adults were extracted from ACTG A5303, a 48‐week randomized clinical trial of two HIV treatment regimens. Participants’ mean (standard deviation) age and years of education were 35.1 (10.7) and 14.3 (2.7) years respectively. Changes from baseline to week 48 of antiretroviral therapy (ART) in individual, total, and domain z‐scores for NP tests and Global Deficit Scores (GDS) were compared between the primary languages using linear regression models, adjusted for baseline scores and years of education.ResultsBaseline demographic characteristics were comparable except Spanish speakers had less years of education than the English speakers (p < 0.001). Although differences in some NP measures and domains were detected at baseline, the adjusted changes in individual, total and domain NP z‐scores from baseline to 48 weeks of ART were not significantly different between the two primary language groups. The 48‐week changes in GDS were also similar.ConclusionChanges in NP during ART were similar between English and Spanish speaking HIV‐infected individuals for all NP measures. This suggests that studies of longitudinal changes in NP can pool participants across these languages.

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Less Bone Loss With Maraviroc- Versus Tenofovir-Containing Antiretroviral Therapy in the AIDS Clinical Trials Group A5303 Study

Abstract: NCT01400412.

Cited by 45 publications

References 38 publications

Bone loss in HIV

Bone loss in HIV

A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy–induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial

Similar changes in neuropsychological functioning in english and spanish speaking HIV patients

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