HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy

Álvarez, Beatriz; Navarrete-Muñoz, María A; Briz, Verónica; Olmedillas‐López, Susana; Nistal, Sara; Cabello, Alfonso; Prieto, Laura Lorente; Górgolas, Miguel; García‐Arranz, Mariano; Benito, José M.; Rallón, Norma

doi:10.1038/s41598-022-08871-0

Cited by 7 publications

(2 citation statements)

References 17 publications

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“…While it has been found that the HIV-1 reservoir remains stable after the administration of DAAs in coinfected subjects [24][25][26], this is the first study carried out in rCD4+ T cells, the main HIV reservoir. Our results contrast with those observed by Álvarez and colleagues [27] who did not observe differences between HIV-monoinfected and -coinfected individuals. Differences relating to patients' inclusion and exclusion criteria, Fiebig stage, time since HIV diagnosis, cells in which proviral DNA was quantified, and the different methodology used could explain the different results.…”

Section: Discussioncontrasting

confidence: 99%

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

Martínez-Román

Crespo-Bermejo

Valle-Millares

et al. 2022

JCM

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Background: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks’ follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+/HCV- spontaneous clarifiers, and 24 HIV+/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load < 50). Viral-spliced RNA transcripts and proviral DNA copies were quantified by qPCR. Paired samples were analyzed using a mixed generalized linear model. Results: A decrease in HIV proviral DNA was observed in HIV+/HCV- subjects, but no significant differences were found for the other study groups. An increased production of multiple spliced transcripts was found in HIV+ and HIV+/HCV+ individuals. Conclusions: We conclude that elimination of HCV by DAAs was unable to revert the consequences derived from chronic HCV infection for the reservoir size and viral splicing, which could indicate an increased risk of rapid HIV-reservoir reactivation. Moreover, spontaneous clarifiers showed a significant decrease in the HIV reservoir, likely due to an enhanced immune response in these individuals.

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Section: Discussioncontrasting

confidence: 99%

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

Martínez-Román

Crespo-Bermejo

Valle-Millares

et al. 2022

JCM

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“…The population included in the present study consisted of HIV-infected patients, who all received successful long-term ART and exhibited high CD4 + T-cell counts. We provide prospective information on pathogenic or immunovirological aspects related to systemic in ammation, T-cell function and homeostasis and reservoir size 30,41,49 for this cohorts of both coinfected and monoinfected individuals.…”

Section: Strengthsmentioning

confidence: 99%

The Era of DAAs: Assessing the Clinical Impact and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals

Álvarez-Álvarez,

Prieto-Pérez,

Cuadra-Grande

et al. 2024

Preprint

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Background Human immunodeficiency virus (HIV) infection causes sustained chronic immune activation which is associated with earlier and more frequent onset of comorbidities. Coinfections, such as those caused by hepatitis C virus (HCV), amplify this immune status. However, direct-acting antivirals (DAAs) transformed HIV/HCV management by eradicating HCV quickly and effectively, bypassing the systemic proinflammatory and immunomodulatory effects of interferon regimens. HCV infection significantly impacts the immunopathogenesis of HIV, and eradication of HCV with DAAs improves, but does not entirely normalize, the levels of markers of systemic inflammation, endothelial dysfunction or T-cell activation and exhaustion. This study aimed to determine whether HIV-infected individuals versus individuals with HIV/HCV coinfection, in the era of interferon-free therapies, exhibit an increased incidence of comorbidities and non-AIDS-related events. Methods A retrospective analysis was conducted at a Spanish tertiary hospital, involving 229 HIV/HCV-coinfected patients and 229 HIV-infected patients, all with effectively controlled HIV. Coinfected patients underwent HCV clearance using DAAs and had no history interferon treatment. The incidences of hypertension, diabetes mellitus, cardiovascular disease, kidney disease, liver disease, non-AIDS cancer and death were compared between the groups. Univariate logistic regression models and subsequent multivariate adjustment for all factors potentially impacting outcomes were used to assess the risk of clinical event onset. Propensity score (PS) analyses were also conducted to support the multivariate model results. Results Univariate logistic regression analyses revealed that, compared to HIV/HCV coinfected patients, HIV monoinfected patients presented a greater risk for hypertension (Odds Ratio [OR] = 1.93; 95% Confidence Interval [CI] = 1.03–3.74; p = 0.040), dyslipidemia (OR = 1.83; 95%CI = 1.13–3.01; p = 0.014) and kidney disease (OR = 3.14; 95%CI = 1.19–9.80; p = 0.019) onset. Monoinfection was also associated with a lower risk for developing liver disease (OR = 0.12; 95%CI = 0.01–0.67; p = 0.012) and death (OR = 0.29; 95%CI = 0.06–0.96; p = 0.043). Multivariate models and PS showed that previous exposure to HCV was not associated with the onset of any clinical events studied. Conclusions Successful HCV elimination using DAAs improved the outlook regarding comorbidities and survival across both patient cohorts. Early HCV detection and DAA therapy could enhance clinical results. These findings provide an optimistic perspective for those living with HIV/HCV coinfection and underscore the importance of continuing efforts toward early detection and DAA treatment initiation.

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HLA-E01:01 allele is associated with better response to anti-HCV therapy while homozygous status for HLA-E01:03 allele increases the resistance to anti-HCV treatments in frequently transfused thalassemia patients

et al. 2022

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HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy

Cited by 7 publications

References 17 publications

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

The Era of DAAs: Assessing the Clinical Impact and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals

HLA-E01:01 allele is associated with better response to anti-HCV therapy while homozygous status for HLA-E01:03 allele increases the resistance to anti-HCV treatments in frequently transfused thalassemia patients

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HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy

Cited by 7 publications

References 17 publications

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance

The Era of DAAs: Assessing the Clinical Impact and Emergence of Comorbidities in HIV/HCV-Coinfected versus HIV-Infected Individuals

HLA-E*01:01 allele is associated with better response to anti-HCV therapy while homozygous status for HLA-E*01:03 allele increases the resistance to anti-HCV treatments in frequently transfused thalassemia patients

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HLA-E01:01 allele is associated with better response to anti-HCV therapy while homozygous status for HLA-E01:03 allele increases the resistance to anti-HCV treatments in frequently transfused thalassemia patients