Abstract

A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (< 400 copies/ml for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR = 0.34 [95% CI 0.29, 0.40] and aOR = 0.48 [95% CI 0.40, 0.57] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.

Details

Title
Clinical factors and outcomes associated with immune non-response among virally suppressed adults with HIV from Africa and the United States
Author
Noiman Adi 1 ; Esber Allahna 2 ; Wang, Xun 3 ; Bahemana Emmanuel 4 ; Adamu Yakubu 5 ; Iroezindu, Michael 5 ; Kiweewa Francis 6 ; Maswai Jonah 7 ; Owuoth, John 8 ; Lucas, Maganga 9 ; Ganesan Anuradha 10 ; Maves, Ryan C 11 ; Lalani Tahaniyat 12 ; Colombo, Rhonda E 13 ; Okulicz, Jason F 14 ; Polyak, Christina 2 ; Crowell, Trevor A 15 ; Ake, Julie A 15 ; Agan, Brian K 3 

 Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525) 
 Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166) 
 Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826) 
 Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166); Henry M. Jackson Foundation MRI, Mbeya, Tanzania (GRID:grid.507680.c) 
 Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166); U.S. Army Medical Research Directorate-Africa, Nairobi, Kenya (GRID:grid.507680.c); Henry M. Jackson Foundation MRI, Abuja, Nigeria (GRID:grid.507680.c) 
 Makerere University Walter Reed Project, Kampala, Uganda (GRID:grid.452639.f) 
 Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166); Kenya Medical Research Institute, Nairobi, Kenya (GRID:grid.33058.3d) (ISNI:0000 0001 0155 5938); Henry M. Jackson Foundation MRI, Kericho, Kenya (GRID:grid.33058.3d) 
 Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166); Kenya Medical Research Institute, Nairobi, Kenya (GRID:grid.33058.3d) (ISNI:0000 0001 0155 5938); Henry M. Jackson Foundation MRI, Kisumu, Kenya (GRID:grid.33058.3d) 
 National Institute of Medical Research-Mbeya Medical Research Centre, Mbeya, Tanzania (GRID:grid.33058.3d) 
10  Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Walter Reed National Military Medical Center, Bethesda, USA (GRID:grid.414467.4) (ISNI:0000 0001 0560 6544) 
11  Naval Medical Center San Diego, San Diego, USA (GRID:grid.415879.6) (ISNI:0000 0001 0639 7318) 
12  Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Naval Medical Center Portsmouth, Portsmouth, USA (GRID:grid.415882.2) (ISNI:0000 0000 9013 4774) 
13  Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, USA (GRID:grid.201075.1) (ISNI:0000 0004 0614 9826); Madigan Army Medical Center, Joint Base Lewis-McChord, USA (GRID:grid.416237.5) (ISNI:0000 0004 0418 9357) 
14  Uniformed Services University of the Health Sciences, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525); Brooke Army Medical Center, San Antonio, USA (GRID:grid.416653.3) (ISNI:0000 0004 0450 5663) 
15  Walter Reed Army Institute of Research, US Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166); Uniformed Services University of the Health Sciences, Division of Infectious Diseases, Department of Medicine, School of Medicine, Bethesda, USA (GRID:grid.265436.0) (ISNI:0000 0001 0421 5525) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2622384891
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.