title: Insulin-Like Growth Factor Is Associated with Changes in Body Composition with Antiretroviral Therapy Initiation.
abstract: Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized clinical trial of ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals from resource-diverse settings. IGF-1 was measured from baseline, week 48, and week 96 stored serum samples. Multivariate models were constructed. 415 participants were included: 170 (41%) were randomized to FTC/TDF+EFV and 245 (59%) to 3TC/ZDV+EFV. The mean age was 35 years, 60% were black, 42% women. The mean IGF-1 level did not change significantly from baseline to week 96 (-0.65 ng/ml; 95% confidence interval (CI) -5.18-3.87), p = .78 and there were no differences by treatment arm at week 96, p = .74. Lower baseline IGF-1 was associated with age, non-white race, greater waist-hip ratio (WHR), low CD4 count, and lower baseline albumin (all p < .01) but not plasma HIV-1 RNA, body mass index, or treatment arm. Greater change in IGF-1 from baseline to 96 weeks was associated with female sex, smaller WHR change, lower baseline albumin, and higher baseline HIV-1 RNA (all p < .01). ART initiation with either ZDV or TDF did not significantly impact overall IGF-1 levels. Baseline and on-treatment changes in IGF-1 with ART initiation may be related to the body composition changes that occur after ART initiation.
authors.affiliation: 1 Department of Medicine, University of Colorado Denver , Aurora, Colorado.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Erlandson
authors.affiliation: 1 Department of Medicine, University of Colorado Denver , Aurora, Colorado.
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Fiorillo
authors.affiliation: 2 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS , Rio de Janeiro, Brazil .
authors.forename: Sandra Wagner
authors.initials: SW
authors.lastname: Cardoso
authors.affiliation: 3 Les Centres GHESKIO , Port-au-Prince, Haiti .
authors.forename: Cynthia
authors.initials: C
authors.lastname: Riviere
authors.affiliation: 4 Asociación Civil Impacta Salud y Educación , Lima, Peru .|5 Department of Global Health, University of Washington , Seattle, Washington.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: 6 Department of Medicine, University of Zimbabwe-College of Health Sciences , Harare, Zimbabwe .
authors.forename: James
authors.initials: J
authors.lastname: Hakim
authors.affiliation: 7 YRGCARE Medical Centre , CART CRS, Chennai, India .
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: 8 Clinical HIV Research Unit, Department of Medicine, University of Witwatersrand , Johannesburg, South Africa .
authors.forename: Sharlaa
authors.initials: S
authors.lastname: Badal-Faesen
authors.affiliation: 9 Durban International Clinical Research Site , Durban, South Africa .
authors.forename: Umesh
authors.initials: U
authors.lastname: Lalloo
authors.affiliation: 10 College of Medicine , Blantyre, Malawi .
authors.forename: Johnstone
authors.initials: J
authors.lastname: Kumwenda
authors.affiliation: 1 Department of Medicine, University of Colorado Denver , Aurora, Colorado.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.affiliation: 11 Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000627:therapeutic use; D001823:Body Composition / Q000502:physiology*; D003521:Cyclopropanes; D004338:Drug Combinations; D000068679:Emtricitabine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D000068698:Tenofovir / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D004338:Drug Combinations; C583557:IGF1 protein, human; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine; D007334:Insulin-Like Growth Factor I; D000068698:Tenofovir; D000068679:Emtricitabine; C098320:efavirenz
keywords: HIV; antiretroviral therapy; highly active; insulin-like growth factor-1; lipodystrophy; obesity