Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection

Thornhill, John; Inshaw, Jamie; Kaleebu, Pontiano; Cooper, David A.; Ramjee, Gita; Schechter, Mauro; Tambussi, Giuseppe; Fox, Julie; Samuel, Miriam; Miró, José M.; Weber, Jonathan; Porter, Kholoud; Fidler, Sarah

doi:10.1097/qai.0000000000001013

Cited by 40 publications

(29 citation statements)

References 30 publications

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“…It is possible that the difference between 24 and 60 weeks of ART is insufficient to observe an effect on the time to rebound. It has also been shown that time from seroconversion to the start of ART is negatively associated with time to rebound and CD4/CD8 ratio normalization (68,70). In this cohort, no difference for time to rebound was observed between participants who were diagnosed during Fiebig stages I-II versus III-IV versus V-VI.…”

Section: Discussionmentioning

confidence: 62%

Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Pasternak¹,

Grijsen²,

Wit³

et al. 2020

JCI Insight

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Section: Discussionmentioning

confidence: 62%

Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Pasternak¹,

Grijsen²,

Wit³

et al. 2020

JCI Insight

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“…To date, few studies have investigated the evolution of CD4/CD8 ratios in patients initiating ART close to infection. A sub-study [28] of the SPARTAC trial [29] investigating factors associated with time from ART initiation to CD4/CD8 ratio normalization, showed a higher probability of CD4/CD8 ratio normalization when ART was initiated closer to seroconversion (within 6 months from seroconversion). More recently, very early ART (initiated within 40 days of the estimated date of infection) in Fiebig I-II acutely infected patients was demonstrated to be associated with a significant increase in CD4/CD8 ratios [14], and the 1-year longitudinal evaluation of 83 patients starting ART within 120 days after the estimated date of infection displayed a better reconstitution of CD4/CD8 ratio compared to chronically infected subjects [15].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection–Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study

Muscatello

Nozza

Fabbiani

et al. 2020

PAI

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Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.Methods: This was an observational, retrospective, and multicenter study. We investigated the effect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virological suppression, optimal immunological recovery (defined as CD4 count ≥ 500/µL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis. Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10copies/mL and the median CD4 count was 456 cells/µL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associated with a shorter time to virological suppression. Early ART emerged as an independent predictor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percentage count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs.Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the beneficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunological markers associated with virological control.

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“…significantly higher likelihood of restoration to normal levels when ART is initiated in the early stages of HIV-1 infection. 35 IFNbased re-treatment in HCV/HIV coinfected patients that had previously failed to achieve an SVR with IFN-based therapy for HCV, demonstrated significantly higher re-treatment SVR rates when patients were successfully HIV-1 RNA suppressed with ART 36 . In the current era where ART is now recommended for all PLWH, 37 the significant numerical and functional restoration of CD4+ T cells that typically occurs with ART, 33 [38][39][40][41] There are three studies in progress for treatment of acute HCV coinfection with grazoprevir/elbasvir with an intended treatment duration of 8 weeks (table 2).…”

Section: Types Of Therapymentioning

confidence: 98%

Interferon-free direct-acting antiviral therapy for acute hepatitis C virus infection in HIV-infected individuals: A literature review

Lampejo

Agarwal

Carey

2018

Digestive and Liver Disease

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Dramatic rises in hepatitis C virus (HCV) coinfection rates in human immunodeficiency virus (HIV)-infected individuals have been observed recently, largely attributable to increasing recreational drug use combined with increased testing for HCV. In the era of direct-acting antiviral (DAA) therapy, treatment of acute HCV infection in HIV-infected individuals with short durations of these drugs may potentially reduce the disease and economic burden associated with HCV infection as well as reducing the likelihood of onward HCV transmission. We performed an extensive literature search of PubMed, Embase and Google Scholar up to 05 September 2017 for clinical trials of acute HCV infection in HIV-infected individuals. In the studies identified, rates of sustained virologic response at 12 weeks post-treatment (SVR12) ranged from 21% with 6 weeks of therapy up to 92% with 12 weeks of therapy with sofosbuvir and ribavirin. Ledipasvir/sofosbuvir for 6 weeks achieved an SVR of 77%. No HIV-related events occurred regardless of whether patients were receiving antiretroviral therapy (ART) and DAAs were well tolerated. Data is currently limited with regards to optimal regimens and durations of therapy, which need to be tailored based on potential interactions with concurrent ART and consideration for the fact that patients with higher baseline HCV RNA levels may require an extended duration of treatment.

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Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 40 publications

References 30 publications

Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection–Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study

Interferon-free direct-acting antiviral therapy for acute hepatitis C virus infection in HIV-infected individuals: A literature review

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