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Infection with HIV-1 subtype D adversely affects the live expectancy independently of antiretroviral drug use

HIV-1 subtypes have been associated with less favourable clinical profiles, differences in disease progression and higher risk of neurocognitive deficit. In this study we aimed to analyse the long term survival disparities between patients infected with the most common HIV-1 variants observed in Pol...

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Published in:Infection, genetics and evolution genetics and evolution, 2021-06, Vol.90, p.104754-104754, Article 104754
Main Authors: Parczewski, Miłosz, Scheibe, Kaja, Witak-Jędra, Magdalena, Pynka, Magdalena, Aksak-Wąs, Bogusz, Urbańska, Anna
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container_title Infection, genetics and evolution
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description HIV-1 subtypes have been associated with less favourable clinical profiles, differences in disease progression and higher risk of neurocognitive deficit. In this study we aimed to analyse the long term survival disparities between patients infected with the most common HIV-1 variants observed in Poland. For the study data from 518 Caucasian non-immigrant patients of Polish origin infected with divergent HIV subtypes and variants [subtype A (n = 35, 6.8%), subtype B (n = 386, 74.5%), subtype C (n = 13, 2.5%), subtype D (n = 58, 11.19%) or other non-A,B,C,D (n = 26, 5.01%)variants] were analysed. Subtyping was performed using the partial pol (reverse transcriptase and protease) sequencing. HIV variant was coupled with clinical, virologic and survival data censored at 20 years of observation. Overall survival and on antiretroviral treatment survival was analysed using Kaplan-Meyer as well as unadjusted and multivariate Cox proportional hazards models. Significantly higher mortality was observed among subtype D (28.8%) infected subjects compared to subtype B (11.7%, p = 0.0004). Increased risk of death among subtype D cases remained significant when cART treated individuals were analysed, with on-treatment mortality of 26.9% for subtype D (p = 0.006) compared to 10.73% in subtype B infected cases. Kaplan-Meyer survival estimates differed significantly across all investigated HIV-1 variant groups when overall 20 year mortality was analysed (log rank p = 0.029), being non-significant for the cART treated group. In multivariate model of overall 20 year survival, adjusted for age at diagnosis, gender, HCV and AIDS status, lymphocyte CD4 count, transmission route and HIV viral load, only age and subtype D were independently associated with higher likelihood of death [HR: 1.08 (95%CI: 1.03–1.14, p = 0.002) and HR: 7.91 (95%CI:2.33–26.86), p 
doi_str_mv 10.1016/j.meegid.2021.104754
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In this study we aimed to analyse the long term survival disparities between patients infected with the most common HIV-1 variants observed in Poland. For the study data from 518 Caucasian non-immigrant patients of Polish origin infected with divergent HIV subtypes and variants [subtype A (n = 35, 6.8%), subtype B (n = 386, 74.5%), subtype C (n = 13, 2.5%), subtype D (n = 58, 11.19%) or other non-A,B,C,D (n = 26, 5.01%)variants] were analysed. Subtyping was performed using the partial pol (reverse transcriptase and protease) sequencing. HIV variant was coupled with clinical, virologic and survival data censored at 20 years of observation. Overall survival and on antiretroviral treatment survival was analysed using Kaplan-Meyer as well as unadjusted and multivariate Cox proportional hazards models. Significantly higher mortality was observed among subtype D (28.8%) infected subjects compared to subtype B (11.7%, p = 0.0004). Increased risk of death among subtype D cases remained significant when cART treated individuals were analysed, with on-treatment mortality of 26.9% for subtype D (p = 0.006) compared to 10.73% in subtype B infected cases. Kaplan-Meyer survival estimates differed significantly across all investigated HIV-1 variant groups when overall 20 year mortality was analysed (log rank p = 0.029), being non-significant for the cART treated group. In multivariate model of overall 20 year survival, adjusted for age at diagnosis, gender, HCV and AIDS status, lymphocyte CD4 count, transmission route and HIV viral load, only age and subtype D were independently associated with higher likelihood of death [HR: 1.08 (95%CI: 1.03–1.14, p = 0.002) and HR: 7.91 (95%CI:2.33–26.86), p &lt; 0.001, respectively]. In the on-treatment (cART) multivariate model of 20 year survival adjusted for the same parameters only subtype D remained as the independent factor associated with higher mortality risk [HR: 4.24 (95%CI:1.31–13.7), p = 0.02]. Subtype D has an independent deleterious effect of survival, even in the setting of antiretroviral treatment. Observed effect indicated higher clinical vigilance for patients infected with this subtype even after long time of stable antiretroviral treatment. •HIV-1 subtype D infection in Caucasian patients is associated with unfavorable clinical and immunologic characteristics.•Infection with this subtype is increases the risk of long-term mortality regardless use of the antiretroviral treatment.•Full mechanism of the higher pathogenicity of the subtype D remains to be elucidated.</description><identifier>ISSN: 1567-1348</identifier><identifier>EISSN: 1567-7257</identifier><identifier>DOI: 10.1016/j.meegid.2021.104754</identifier><identifier>PMID: 33540086</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Female ; HIV Infections - mortality ; HIV Infections - virology ; HIV-1 - physiology ; Humans ; Life Expectancy ; Male ; Middle Aged ; Mortality risk ; Poland - epidemiology ; Subtype D ; Survival</subject><ispartof>Infection, genetics and evolution, 2021-06, Vol.90, p.104754-104754, Article 104754</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. 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Increased risk of death among subtype D cases remained significant when cART treated individuals were analysed, with on-treatment mortality of 26.9% for subtype D (p = 0.006) compared to 10.73% in subtype B infected cases. Kaplan-Meyer survival estimates differed significantly across all investigated HIV-1 variant groups when overall 20 year mortality was analysed (log rank p = 0.029), being non-significant for the cART treated group. In multivariate model of overall 20 year survival, adjusted for age at diagnosis, gender, HCV and AIDS status, lymphocyte CD4 count, transmission route and HIV viral load, only age and subtype D were independently associated with higher likelihood of death [HR: 1.08 (95%CI: 1.03–1.14, p = 0.002) and HR: 7.91 (95%CI:2.33–26.86), p &lt; 0.001, respectively]. 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In this study we aimed to analyse the long term survival disparities between patients infected with the most common HIV-1 variants observed in Poland. For the study data from 518 Caucasian non-immigrant patients of Polish origin infected with divergent HIV subtypes and variants [subtype A (n = 35, 6.8%), subtype B (n = 386, 74.5%), subtype C (n = 13, 2.5%), subtype D (n = 58, 11.19%) or other non-A,B,C,D (n = 26, 5.01%)variants] were analysed. Subtyping was performed using the partial pol (reverse transcriptase and protease) sequencing. HIV variant was coupled with clinical, virologic and survival data censored at 20 years of observation. Overall survival and on antiretroviral treatment survival was analysed using Kaplan-Meyer as well as unadjusted and multivariate Cox proportional hazards models. Significantly higher mortality was observed among subtype D (28.8%) infected subjects compared to subtype B (11.7%, p = 0.0004). Increased risk of death among subtype D cases remained significant when cART treated individuals were analysed, with on-treatment mortality of 26.9% for subtype D (p = 0.006) compared to 10.73% in subtype B infected cases. Kaplan-Meyer survival estimates differed significantly across all investigated HIV-1 variant groups when overall 20 year mortality was analysed (log rank p = 0.029), being non-significant for the cART treated group. In multivariate model of overall 20 year survival, adjusted for age at diagnosis, gender, HCV and AIDS status, lymphocyte CD4 count, transmission route and HIV viral load, only age and subtype D were independently associated with higher likelihood of death [HR: 1.08 (95%CI: 1.03–1.14, p = 0.002) and HR: 7.91 (95%CI:2.33–26.86), p &lt; 0.001, respectively]. In the on-treatment (cART) multivariate model of 20 year survival adjusted for the same parameters only subtype D remained as the independent factor associated with higher mortality risk [HR: 4.24 (95%CI:1.31–13.7), p = 0.02]. Subtype D has an independent deleterious effect of survival, even in the setting of antiretroviral treatment. Observed effect indicated higher clinical vigilance for patients infected with this subtype even after long time of stable antiretroviral treatment. •HIV-1 subtype D infection in Caucasian patients is associated with unfavorable clinical and immunologic characteristics.•Infection with this subtype is increases the risk of long-term mortality regardless use of the antiretroviral treatment.•Full mechanism of the higher pathogenicity of the subtype D remains to be elucidated.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33540086</pmid><doi>10.1016/j.meegid.2021.104754</doi><tpages>1</tpages></addata></record>
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subjects Adult
Female
HIV Infections - mortality
HIV Infections - virology
HIV-1 - physiology
Humans
Life Expectancy
Male
Middle Aged
Mortality risk
Poland - epidemiology
Subtype D
Survival
title Infection with HIV-1 subtype D adversely affects the live expectancy independently of antiretroviral drug use
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