TY - JOUR
T1 - Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens
T2 - A prospective RESPOND cohort study
AU - Álvarez, Hortensia
AU - Mocroft, Amanda
AU - Ryom, Lene
AU - Neesgaard, Bastian
AU - Edwards, Simon
AU - Svedhem, Vero-Nica
AU - Günthard, Huldrych F
AU - Zangerle, Robert
AU - Smith, Colette
AU - Castagna, Antonella
AU - D Arminio Monforte, Antonella
AU - Wit, Ferdinand
AU - Stecher, Melanie
AU - Lehman, Clara
AU - Mussini, Cristina
AU - Fontas, Eric
AU - González, Eva
AU - Wasmuth, Jan-Christian
AU - Sönnerborg, Anders
AU - De Wit, Stéphane
AU - Chkhartishvili, Nikoloz
AU - Stephan, Christoph
AU - Petoumenos, Kathy
AU - Jaschinski, Nadine
AU - Vannappagari, Vani
AU - Gallant, Joel
AU - Young, Lital
AU - Volny Anne, Alain
AU - Greenberg, Lauren
AU - Martín-Iguacel, Raquel
AU - Poveda, Eva
AU - Llibre, Josep M
AU - RESPOND (International Cohort Consortium of Infectious Diseases) Study Group
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2023/8/22
Y1 - 2023/8/22
N2 - BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort.METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression.RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs.CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.
AB - BACKGROUND: There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort.METHODS: We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression.RESULTS: Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs.CONCLUSIONS: Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.
KW - Anti-HIV Agents/therapeutic use
KW - CD4-Positive T-Lymphocytes
KW - Cohort Studies
KW - HIV Infections/drug therapy
KW - HIV Integrase Inhibitors/therapeutic use
KW - HIV-1/genetics
KW - Humans
KW - Prospective Studies
KW - RNA/therapeutic use
KW - Viral Load
KW - Viremia/drug therapy
KW - integrase inhibitors
KW - low-level viremia
KW - residual viremia
KW - virological failure
KW - blip
UR - http://www.scopus.com/inward/record.url?scp=85170276524&partnerID=8YFLogxK
U2 - 10.1093/cid/ciad219
DO - 10.1093/cid/ciad219
M3 - Journal article
C2 - 37052343
SN - 1058-4838
VL - 77
SP - 593
EP - 605
JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
IS - 4
ER -