Long-term safety and efficacy of atazanavir-based therapy in HIV-infected infants, children and adolescents: the Pediatric AIDS Clinical Trials Group Protocol 1020A
Richard M Rutstein, Pearl Samson, Terry Fenton, Courtney V Fletcher, Jennifer J Kiser, Lynne M Mofenson, Elizabeth Smith, Bobbie Graham, Marina Mathew, Grace Aldrovani, PACTG 1020A Study Team, Richard M Rutstein, Steven Douglas, Grace Aldrovandi, Jennifer Kiser, Courtney V Fletcher, Terence Fenton, Pearl Samson, Bobbie Graham, Heather L Sprenger, Lynne M Mofenson, Elizabeth Smith, Lynette Purdue, Catherine Kneut, Betto Ortiz, Quianna Douglas, Elizabeth Petzold, Tammy Myers, Avye Violari, Glenda Gray, Mariaaranxta Horga, Steven Schnittman, Marina Matthew, Arry Dieudonne, Juliette Johnson, Lisa Monti, Yvonne Bryson, Jaime G Deville, Karin Nielsen-Saines, Mary Paul, Hunter Hammill, Chivon McMullen-Jackson, Ram Yogev, Eric Cagwin, Ruth Williams, Stephen A Spector, Rolando M Viani, Lisa Stangl, John Swetnam, Joan Wilson, Margaret Donnelly, Elaine Abrams, Maxine Frere, Delia Calo, Stephen I Pelton, Deb McLaud, Lisa Tucker, William Borkowsky, Aditya Kaul, Nagamah Deygoo, Andrew Wiznia, Marlene Burey, Karen Kassen, Lisa M Frenkel, Ann J Melvin, Kathleen M Mohan, Randall Fisher, Donna Sandifer, Mednela Acevedo-Flores, Odette Garcias-Vina, Lizbeth M Fabregas, Wanda Figueroa, Priya Guyadeen, Maureen Famiglietti Butler, Kathie Contello, Wendy Holz, Octavio Ramilo, Anna Winborn, Sohail Rana, Patricia Houston, Jhoanna Roa, Andrea Kovacs, James Homans, LaShonda Spencer, Myron Levin, Elizabeth Mcfarland, Emily Barr, Ana M Puga, Zulma Eysallenne, Kathleen Graham, James B McAuley, Maureen McNichols, Latnia Logan, Diane Wara, Mica Muscat, Nicole Tilton, Janathan Ellen, Allison Agwu, Laurel Borkovic, Audra Deveikis, Jagmohan Batra, Janielle Jackson Alvarez, John Farley, Douglas Watson, Kimberly Klipner, Russell Vandyke, Margarita Silio, Cheryl A Borne, Robert F Pass, Marilyn J Crain, Newana Beatty, Patricia Flynn, Nehali Patel, Marlon Donohoe, Richard M Rutstein, Steven Douglas, Carol A Vincent, Jill Foster, Janet Chen, Patricia C Coburn, Murli Purswani, Stefan Hagmann, Mary-Elizabeth Vachon, Katherine Luzuriaga, Margaret McManus, Donna Christian, Authur Provisor, Anita Whitten, Dawn Barnes, Tammy Meyers, Harry Moultrie, Hermien Gous, Avy Violari, Nasreen Abrahams, Afaaf Liberty, Richard M Rutstein, Pearl Samson, Terry Fenton, Courtney V Fletcher, Jennifer J Kiser, Lynne M Mofenson, Elizabeth Smith, Bobbie Graham, Marina Mathew, Grace Aldrovani, PACTG 1020A Study Team, Richard M Rutstein, Steven Douglas, Grace Aldrovandi, Jennifer Kiser, Courtney V Fletcher, Terence Fenton, Pearl Samson, Bobbie Graham, Heather L Sprenger, Lynne M Mofenson, Elizabeth Smith, Lynette Purdue, Catherine Kneut, Betto Ortiz, Quianna Douglas, Elizabeth Petzold, Tammy Myers, Avye Violari, Glenda Gray, Mariaaranxta Horga, Steven Schnittman, Marina Matthew, Arry Dieudonne, Juliette Johnson, Lisa Monti, Yvonne Bryson, Jaime G Deville, Karin Nielsen-Saines, Mary Paul, Hunter Hammill, Chivon McMullen-Jackson, Ram Yogev, Eric Cagwin, Ruth Williams, Stephen A Spector, Rolando M Viani, Lisa Stangl, John Swetnam, Joan Wilson, Margaret Donnelly, Elaine Abrams, Maxine Frere, Delia Calo, Stephen I Pelton, Deb McLaud, Lisa Tucker, William Borkowsky, Aditya Kaul, Nagamah Deygoo, Andrew Wiznia, Marlene Burey, Karen Kassen, Lisa M Frenkel, Ann J Melvin, Kathleen M Mohan, Randall Fisher, Donna Sandifer, Mednela Acevedo-Flores, Odette Garcias-Vina, Lizbeth M Fabregas, Wanda Figueroa, Priya Guyadeen, Maureen Famiglietti Butler, Kathie Contello, Wendy Holz, Octavio Ramilo, Anna Winborn, Sohail Rana, Patricia Houston, Jhoanna Roa, Andrea Kovacs, James Homans, LaShonda Spencer, Myron Levin, Elizabeth Mcfarland, Emily Barr, Ana M Puga, Zulma Eysallenne, Kathleen Graham, James B McAuley, Maureen McNichols, Latnia Logan, Diane Wara, Mica Muscat, Nicole Tilton, Janathan Ellen, Allison Agwu, Laurel Borkovic, Audra Deveikis, Jagmohan Batra, Janielle Jackson Alvarez, John Farley, Douglas Watson, Kimberly Klipner, Russell Vandyke, Margarita Silio, Cheryl A Borne, Robert F Pass, Marilyn J Crain, Newana Beatty, Patricia Flynn, Nehali Patel, Marlon Donohoe, Richard M Rutstein, Steven Douglas, Carol A Vincent, Jill Foster, Janet Chen, Patricia C Coburn, Murli Purswani, Stefan Hagmann, Mary-Elizabeth Vachon, Katherine Luzuriaga, Margaret McManus, Donna Christian, Authur Provisor, Anita Whitten, Dawn Barnes, Tammy Meyers, Harry Moultrie, Hermien Gous, Avy Violari, Nasreen Abrahams, Afaaf Liberty
Abstract
Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses.
Methods: Antiretroviral-naïve and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa.
Results: Of 195 children enrolled, 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose; 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%) had HIV RNA ≤ 400 cpm. At week 48, 69.5% of naïve and 43.3% of experienced subjects had HIV RNA ≤ 400 cpm; median CD4 increase was 196.5 cells/mm. The primary adverse event (AE) was increased serum bilirubin; 9% of subjects had levels ≥ 5.1 times upper limit of normal (ULN) and 1.4% noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1% at baseline to 5.7%.
Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.
Source: PubMed