OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN: Patients were treated and monitored according to Italian guidelines. For the description of cases, the percentage of CD8CD38HLA*DR cells, CD8CD38HLA*DR cells, major histocompatibility complex genotyping, total HIV-DNA and plasma levels of anti-retroviral (ARV) drugs were performed. RESULTS: Patients started therapy during chronic infection. Patient 26636 started her first ARV drug two years after diagnosis and patients 93016 and 50293 started cART with high viral loads and low CD4 cell counts. Time without cART was 13, 11 and 1.5 years, respectively. None presented any of the protective class I HLA alleles and patient 93016 has the HLA-B*35 allele that appears to be enriched in PTCs. Patients 93016 and 50293 had very low levels of CD8CD38HLA*DR cells (<5%) much lower than those of patient 26636 (27%). T-cell-associated HIV-DNA was 3.78, 3.48 and 3.13 log copies/10 CD4, respectively. CONCLUSION: Patients like ours may advance our understanding of the characteristics for which individuals may be more likely to achieve ART-free remissions. Furthermore, our patients are among the few so far described who started cART during chronic infection extending the hope that a functional cure is possible even in this setting.
OBJECTIVE: Control HIV replication requires continuous combined antiretroviral therapy (cART) as discontinuation of cART results in a rapid viral rebound. However, a few individuals exist who took cART for several years and did not show the expected viral rebound after treatment cessation. Most post-treatment controllers (PTCs) are early treated individuals. We report three cases who started cART during chronic infection. DESIGN:Patients were treated and monitored according to Italian guidelines. For the description of cases, the percentage of CD8CD38HLA*DR cells, CD8CD38HLA*DR cells, major histocompatibility complex genotyping, total HIV-DNA and plasma levels of anti-retroviral (ARV) drugs were performed. RESULTS:Patients started therapy during chronic infection. Patient 26636 started her first ARV drug two years after diagnosis and patients 93016 and 50293 started cART with high viral loads and low CD4 cell counts. Time without cART was 13, 11 and 1.5 years, respectively. None presented any of the protective class I HLA alleles and patient 93016 has the HLA-B*35 allele that appears to be enriched in PTCs. Patients 93016 and 50293 had very low levels of CD8CD38HLA*DR cells (<5%) much lower than those of patient 26636 (27%). T-cell-associated HIV-DNA was 3.78, 3.48 and 3.13 log copies/10 CD4, respectively. CONCLUSION:Patients like ours may advance our understanding of the characteristics for which individuals may be more likely to achieve ART-free remissions. Furthermore, our patients are among the few so far described who started cART during chronic infection extending the hope that a functional cure is possible even in this setting.
Authors: Radwa Sharaf; Guinevere Q Lee; Xiaoming Sun; Behzad Etemad; Layla M Aboukhater; Zixin Hu; Zabrina L Brumme; Evgenia Aga; Ronald J Bosch; Ying Wen; Golnaz Namazi; Ce Gao; Edward P Acosta; Rajesh T Gandhi; Jeffrey M Jacobson; Daniel Skiest; David M Margolis; Ronald Mitsuyasu; Paul Volberding; Elizabeth Connick; Daniel R Kuritzkes; Michael M Lederman; Xu G Yu; Mathias Lichterfeld; Jonathan Z Li Journal: J Clin Invest Date: 2018-08-20 Impact factor: 14.808
Authors: Golnaz Namazi; Jesse M Fajnzylber; Evgenia Aga; Ronald J Bosch; Edward P Acosta; Radwa Sharaf; Wendy Hartogensis; Jeffrey M Jacobson; Elizabeth Connick; Paul Volberding; Daniel Skiest; David Margolis; Michael C Sneller; Susan J Little; Sara Gianella; Davey M Smith; Daniel R Kuritzkes; Roy M Gulick; John W Mellors; Vikram Mehraj; Rajesh T Gandhi; Ronald Mitsuyasu; Robert T Schooley; Keith Henry; Pablo Tebas; Steven G Deeks; Tae-Wook Chun; Ann C Collier; Jean-Pierre Routy; Frederick M Hecht; Bruce D Walker; Jonathan Z Li Journal: J Infect Dis Date: 2018-11-05 Impact factor: 5.226
Authors: Avy Violari; Mark F Cotton; Louise Kuhn; Diana B Schramm; Maria Paximadis; Shayne Loubser; Sharon Shalekoff; Bianca Da Costa Dias; Kennedy Otwombe; Afaaf Liberty; James McIntyre; Abdel Babiker; Diana Gibb; Caroline T Tiemessen Journal: Nat Commun Date: 2019-01-24 Impact factor: 14.919