Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study
Authors: Álvarez Hortensia , Mocroft Amanda , Ryom Lene , Neesgaard Bastian , Edwards Simon , Svedhem Veronica , Günthard Huldrych F , Zangerle Robert , Smith Colette , Castagna Antonella , d’Arminio Monforte Antonella , Wit Ferdinand , Stecher Melanie , Lehman Clara , Mussini Cristina , Fontas Eric , González Eva , Wasmuth Jan-Christian , Sönnerborg Anders , De Wit Stéphane , Chkhartishvili Nikoloz , Stephan Christoph , Petoumenos Kathy , Jaschinski Nadine , Vannappagari Vani , Gallant Joel , Young Lital , Volny Anne Alain , Greenberg Lauren , Martín-Iguacel Raquel , Poveda Eva , Llibre Josep M ,   for the RESPOND (International Cohort Consortium of Infectious Diseases) Study Group, Wit F , Valk M v d , Hillebregt M , Petoumenos K , Law M , Byonanebye D , Hutchinson J , Zangerle R , Appoyer H , Vera J , Clarke A , Broster B , Barbour L , De Wit S , Delforge M , Begovac J , Wandeler G , Stephan C , Bucht M , Chkhartishvili N , Chokoshvili O , d’Arminio Monforte A , Rodano A , Tavelli A , Fanti I , Mussini C , Borghi V , Pradier C , Fontas E , Dollet K , Caissotti C , Casabona J , Miro J M , Smith C , Lampe F , Johnson M , Burns F , Chaloner C , Castagna A , Lazzarin A , Poli A , Sönnerborg A , Falconer K , Svedhem V , Günthard H F , Ledergerber B , Bucher H , Kusejko K , Wasmuth J C , Rockstroh J , Vehreschild J J , Fätkenheuer G , Scherer M , Schulze N , Franke B , Ryom L , Law M , Rooney J , McNicholl I , Vannappagari V , Garges H , Petoumenos K , Wandeler G , Zangerle R , Smith C , De Wit S , Lundgren J , Günthard H F , Young L , Campo R , Lundgren J , Günthard H F , Kowalska J , Raben D , Ryom L , Mocroft A , Rockstroh J , Peters L , Kirk O , Podlekareva D , Volny Anne A , Dedes N , Williams E D , Chkhartishvili N , Zangerle R , Petoumenos K , Law M , Wit F , Necsoi C , Wandeler G , Stephan C , Pradier C , d’Arminio Monforte A , Mussini C , Bruguera A , Bucher H , Sönnerborg A , Vehreschild J J , Wasmuth J C , Smith C , Castagna A , Vera J , Begovac J , Rooney J , McNicholl I , Vannappagari V , Garges H , Young L , Campo R , Ryom L , Mocroft A , Neesgaard B , Greenberg L , Jaschinski N , Bansi-Matharu L , Svedhem-Johansson V , Wit F , Grabmeier-Pfistershammer K , Zangerle R , Hoy J , Bloch M , Braun D , Calmy A , Schüttfort G , Youle M , De Wit S , Mussini C , Zona S , Castagna A , Antinori A , Chkhartishvili N , Bolokadze N , Fontas E , Dollet K , Pradier C , Miro J M , Llibre J M , Vehreschild J J , Schwarze-Zander C , Wasmuth J C , Rockstroh J , Petoumenos K , Law M , Duvivier C , Dragovic G , Radoi R , Oprea C , Vasylyev M , Kowalska J , Matulionyte R , Mulabdic V , Marchetti G , Kuzovatova E , Coppola N , Begovac J , Aho I , Martini S , Bucher H , Harxhi A , Wæhre T , Pharris A , Vassilenko A , Fätkenheuer G , Bogner J , Maagaard A , Jablonowska E , Elbirt D , Marrone G , Leen C , Wyen C , Kundro M , Hathleberger C , Pelchen-Matthews A , Byonanebye D , Fursa O , Roen A , Dahlerup-Rasmussen L , Dedes N , Dixon Williams E , Gallant J , Thorpe D , Vannappagari V , Garges H , Arduino J M , Sklar P , Anne Alain Volny , Dedes Nikos , Mendão Luis , Williams Esther Dixon , Larsen J F , Neesgaard B , Jaschinski N , Fursa O , Valdemaier O , Timiryasova A , Ryom L , Peters L , Jakobsen M L , Kraef C , Gardizi M , Raben D , Elsing T W , Ramesh Kumar L , Shahi S , Andersen K , Reekie J , Mocroft A , Greenberg L , Bansi-Matharu L , Pelchen-Matthews A , Petoumenos K , Byonanebye D , Tusch E , Roen A , Bannister W 
Published: April 2023

Abstract

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 &gt;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.